Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Significant isospin effects are observed by the HADES collaboration in inclusive dilepton production channels in the pp and quasi free np experiments at 1.25 GeV kinetic beam energy. Triggered by this observation, analyses of several exclusive channels within either dilepton or pion production have been started to shed more light on the possible explanations. Furthermore, the exclusive p⁺p⁻ production in np and pp collisions provide tests for a consistent description of double pion production in different isospin states, which is necessary to understand contributions of the double Δ(1232) and N^*(1440) production. This is also important in the context of the recent results from the WASA collaboration on the ABC effect with reference to a d* dibaryon resonance in isospin 0 channel.

Introduction
The epidermal growth factor receptor (EGFR) plays a critical role in epithelial tumors and, therefore, is a promising target for both tumor imaging and therapy. In order to develop novel EGFR-targeted radiotracers/radiotherapeutics the present work aims at synthesis of structurally modified recombinant EGF. One strategy implies incorporation of azidohomoalanine instead of methionine using supplementation-based incorporation by E. coli. Consequently, the biomolecule can be labeled site-selectively by Click reaction (Huisgen 1,3-dipolar cycloaddition) with fluorescence and radiolabeled building blocks, respectively.

Method and Results
The EGF gene motif was successfully ligated into vectors containing either a GST-tag or His6-tag. Resulting plasmids were transformed into methionine-auxotrophic E. coli (B834(DE3)pLysS), protein synthesis under addition of azidohomoalanine and protein purification were established. Purification of the GST fusion protein only resulted in the unmodified protein, but not in the azido-functionalized protein. In contrast, purification of His6-tagged azido-functionalized EGF was successfully established. This could be demonstrated by reaction with various alkynylated fluorescent dyes. Moreover, the modified EGF was radiolabeled with 1-(but-3-inyl)-4-(3-[18F]fluoropropyl)piperazine ([18F]BFP) as the alkyne with a radiochemical yield of about 0.5 % using Click reaction. First cell binding studies of [18F]BFP-labeled EGF demonstrated cellular association in EGFR-overexpressing A431 human epidermoid carcinoma cells. Cellular uptake amounted to about 25 % of injected dose/mg protein after 1 hour at 37°C.

Conclusion
Ongoing work focuses on the optimization of site-selective radiolabeling of EGF by Click reaction with higher radiochemical yield and specific activity. Afterwards, the radiolabeled protein will be radiopharmacologically tested concerning its properties as potential radiotracer.

There is currently a great interest in the application of nanoparticles for molecular imaging. This results in the development of both, organic and inorganic nanoparticles functionalized in a way that radionuclides, targeting ligands, and different biopolymers can be attached in order to provide an imaging signal. Ultrasmall superparamagnetic iron oxide (Fe3O4) nanoparticles (USPIOs) are one of the most widely studied nanomaterials. USPIOs possess unique magnetic properties that make them attractive candidates as advanced biomedical materials (1).
Furthermore, the biocompatibility of USPIOs makes them suitable to be used as multifunctional agents. They can serve as contrast agents for clinical use in magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging (OI) (2).
This work aims at the development of new nanotracers based on USPIOs coated with a biodegradable polymer that are also decorated with agents for radiochemical and/or fluorescence imaging and Epidermal Growth Factor Receptor-specific ligands as targeting units (3).
The production of hydrophobic USPIOs has been achieved using thermal decomposition and monodisperse nanocrystals within a size of 4-5 nm were observed with Transmission electron microscopy (TEM) (4). The main limitation of using USPIOs for in vivo applications is their instability in water. Different biocompatible polymers such as polyvinylalcohol and polyacrylic acid have been tested for the hydrophilic coating of the iron oxide core to make them stable in aqueous solution (5). After an intensive physicochemical characterization including studies of their stability in water and several buffers, carboxymethyl polyvinyl alcohol (CMPVA) was chosen as the most suitable coating agent for the surface modification of USPIOs (6). The stability of the CMPVA-coated USPIOs was studied using Dynamic Light Scattering (DLS, Zetasizer/ Malvern).
Our first goal was to engineer and functionalize the surface of the hydrophilic USPIOs. This included the attachment of a fluorescent label to the shell. This enabled the USPIOs to be suitable for fluorescence imaging. Furthermore, preliminary radiolabeling studies (64Cu) have been undertaken using USPIOs decorated with functional copper chelating agents, such as NOTA. Radio-HPLC and Radio-TLC have been applied to get information about the labelling efficiency and stability of the 64Cu-labeled USPIOs.
From our point of view, the generated nanoparticles possess promising features as novel imaging agents for in vivo cancer diagnostics.

1. Barreto, J.A., et al. Advanced Materials, 23(12): p. H18-H40, 2011.
2. Laurent, S., et al., Chemical Reviews, 108(6): p. 2064-211, 2008.
3. Li, Z., et al., The FASEB Journal, 19(14): p. 1978-1985, 2005..
4. Park, J., et al., Nat Mater, 3(12): p. 891-895, 2004.
5. Zhang, F., et al., Small, 7(22): p. 3113-3127, 2011.
6. Liong, M., et al., Advanced Materials, 22(45): p. 5168-5172, 2010.

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A novel program package has been developed which allows for the simultaneous treatment of atomistic kinetics in collision cascades caused by energetic ion impacts and thermally activated relaxation and diffusion. In this 3D program named TRIDER (TRansport of Ions in matter with DEfect R}elaxation) the collision cascades treated in the framework of the Binary Collision Approximation has been combined with kinetic lattice Monte-Carlo simulations of the atomistic relaxation and diffusion. TRIDER simulations allow a more realistic description of ion-induced surface patterning because subsurface defect kinetics can be included in the simulations, which is demonstrated for low-energy Ar+ ion irradiation of silicon. The deeper understanding of ion beam mixing of bimetal interfaces can also be achieved: it is shown that the conventional Gaussian mixing profile is changed substantially for immiscible metals due to precipitation and for chemically active metals due to formation of intermetallics of different stoichiometry.

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The production of strongly magnetized laser plasmas, of interest for laboratory astrophysics and inertial confinement fusion studies, is presented. This is achieved by coupling a 16 kV pulse-power system. This is achieved by coupling a 16 kV pulse-power system, which generates a magnetic field by means of a split coil, with the ELFIE laser facility at Ecole Polytechnique. In order to influence the plasma dynamics in a significant manner, the system can generate, repetitively and without debris, high amplitude magnetic fields (40 T) in a manner compatible with a high-energy laser environment. A description of the system and preliminary results demonstrating the possibility to magnetically collimate plasma jets are given.

Following our recent letter [1] on inclusive e+e− pair production in proton induced reactions at Ekin = 3.5 GeV on the nucleus Nb, we present here in addition the transverse and rapidity distributions for various e+e− invariant mass bins and compare them to reference data measured in p+p reactions.

Fe(II)-bearing phases are naturally occuring in most anoxic aquifers, and form also at the surface of corroding steel containers under typical nuclear waste repository conditions. Due to their ability to reduce metal and metalloid contaminants, they are expected to play a key role for the migration behaviour of a wide range of radionuclides, including actinides and fission products. Using X-ray absorption spectroscopy as main tool, we have studied reaction end products, mechanisms and kinetics of redox processes at a range of water/mineral interfaces, including magnetite, green rust, mackinawite, chukanovite, and Fe2+-sorbed clays, but also in more redox-inert systems like cement.
Our results show that the electron transport within mineral structures and at the surface is controlling the extent and the kinetics of multi-electron redox reactions.

Magnetite, which forms under anoxic conditions on the surface of corroding steel containers, is able to reduce a range of elements, including radionuclides of high relevance in the context of nuclear waste disposal, e.g. Se, Tc, U, Np, Pu [1]. Aqueous Pu(V) is rapidly reduced by nanoparticulate magnetite to Pu(III), which then forms stable, tridentate sorption complexes on the {111} faces of magnetite [2]. Trivalent lanthanides have been shown to substitute for Fe(III) in magnetite, although their ionic radii are about 1.4 times larger than that of Fe(III) (1.15-1.17 vs. 0.79 Å in six-fold coordination) [3]. To investigate if such an incorporation is also possible for Pu(III) with a similar ionic radius as the lanthanides, we conducted coprecipitation experiments with two Pu loadings of 1000 and 3500 ppm. UV-VIS spectroscopy showed an immediate reduction of Pu(V) to Pu(III) in the initial Fe(II)/Fe(III) chloride solution. After formation of the black magnetite precipitate, Pu(III) concentration in solution was below 10-9 M. X-ray Absorption Near-Edge Structure (XANES) spectroscopy confirmed the trivalent oxidation state of solid phase-associated Pu. Extended X-ray Absorption Fine-Structure (EXAFS) spectroscopy was then used to investigate the molecular structure of incorporated Pu(III) in the fresh precipitate as well as after Fe(II)-induced aging [4]. The EXAFS spectra revealed two different spectral components. The first component represents the tridentate Pu(III) sorption complex also observed during sorption experiments. The second component represents Pu(III) in a highly distorted magnetite Oh site. The proportion of the incorporated Pu(III) decreased from about 75% to 40% with Fe(II)-induced aging, while the proportion of sorbed Pu(III) increased correspondingly. Our results suggest, therefore, that Pu can be incorporated by magnetite, but will convert to sorbed species on the long time scales relevant for nuclear waste disposal.

[1] Scheinost et al. (2008) J. Contam. Hydrol. 102, 228-245. [2] Kirsch et al. (2011), Environ. Sci. Technol. 45, 7267–7274. [3] Moon et al. (2007) Extremophiles 11, 859-867. [4] Boland et al. (2011) Environ. Sci. Technol. 45, 1327-1333.

For the redox-reactive fission products and actinides Se, Tc, U, and Np, it is assumed that the strongly reducing conditions in deep underground, anoxic nuclear waste repositories will reduce their mobility, since their lower-oxidation states commonly form solids of very low solubility. This is not necessarily the case for Pu, where the hexa- and pentavalent aquo-complexes prevalent at higher pe are replaced at lower pe by a tetravalent solid of low solubility, PuO2, but also by a trivalent aquocomplex at lower pH (Fig. 1) [1, 2]. Since the predominance field of Pu(III)aq overlaps with that obtained for the Fe(II)/Fe(III) redox couple as aqueous species or in equilibrium with Fe(II)-bearing minerals [3], one should assume that Pu(III) exists under anoxic nuclear waste conditions, where Fe(II) sources are provided by corroding steel containers and Fe(II)-bearing clays used as confinement, as well as by geogenic minerals. Although some studies have previously reported on trivalent lanthanides, little is known on the retention mechanisms of the trivalent Pu aquo complex by minerals, with implications for the safety case of nuclear waste repositories.

Melanoma is the most malignant type of all skin neoplasms. Although current clinical, morphologic, pathologic, and biochemical methods provide insights into disease behavior and outcome, melanoma is still an unpredictable disease. Once in an advanced stage, it remains a fatal neoplasm with scarce therapeutic options. Therefore, significant efforts still need to be made in finding suitable biomarkers that could aid or improve its early diagnosis, its correct staging, the discrimination of other pathological conditions as well as indicate patients’ prognosis or the most appropriate therapeutic regimes. On the other hand, well-defined diagnostic markers are necessary to avoid the apparent overdiagnosis of melanoma.

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[¹⁸F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([¹⁸F]FSA) as a novel aromatic sulfonamide-based click chemistry building block. [¹⁸F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [¹⁸F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [¹⁸F]F-SA as click chemistry building blockwas demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 %(HSA), and 25 %(L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for ¹⁸F labeling of biopolymers, Cu(I)-mediated click chemistry with [¹⁸F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter ¹⁸F.

Complexation of [UO2]2+ with Cl−, Br−, and I− in N,N-dimethylformamide (DMF) was studied by UV-vis absorption spectroscopy and extended X-ray absorption fine structure (EXAFS) to clearly differentiate halide coordination strengths to [UO2]2+. In the Cl− system, it was clarified that the Cl− coordination to [UO2]2+ in DMF proceeds almost quantitatively. The coordination number of Cl− increases up to 4 with increasing its total concentration, i.e., the limiting complex is [UO2Cl4]2−. Logarithmic gross stability constants of [UO2Clx]2−x (x = 1-4) were evaluated as log 1 = 9.67, log 2 = 15.49, log 3 = 19.89, and log 4 = 24.63 from UV-vis titration experiment. The EXAFS results well demonstrated not only the Cl− coordination, but also the DMF solvation in the equatorial plane of [UO2]2+. The similar experiments were also performed for the Br− and I− systems. As a result, the Br− coordination to [UO2]2+ stops at the second step, i.e., only [UO2Br]+ and UO2Br2 were observed. The molecular structure of each occurring species was confirmed by EXAFS. The evaluated log x of [UO2Brx]2−x (x = 1, 2) are 3.45 and 5.42, respectively. The much smaller log x than those of [UO2Clx]2−x indicates that Br− is much weaker ligand to [UO2]2+ than Cl−. The EXAFS experiments revealed that the presence of I− in the test solution does not modify any coordination structure around [UO2]2+. Thus, I− does not form any stable [UO2]2+ complexes in DMF. Consequently, the stability of the halido complexes of [UO2]2+ in DMF is exactly in line with the hardness order of halides. This trend clearly manifests the hardness of [UO2]2+.

Cerium(III) and cerium(IV) form both formate complexes. However, their species in aqueous solution and the solid-state structures are surprisingly different. The species in aqueous solutions were investigated with Ce K-edge EXAFS spectroscopy. Ce(III) formate shows only mononuclear complexes, which is in agreement with the predicted mononuclear species of Ce(HCOO)2+ and Ce(HCOO)2+. In contrast, Ce(IV) formate forms in aqueous solution a stable hexanuclear complex of [Ce6(μ3-O)4(μ3-OH)4(HCOO)x(NO3)y]12-x-y. The structural differences reflect the different influence of hydrolysis, which is weak for Ce(III) and strong for Ce(IV). Hydrolysis of Ce(IV) ions causes initial polymerization while complexation through HCOO- results in 12 chelate rings stabilizing the hexanuclear Ce(IV) complex.
Crystals were grown from the above mentioned solutions. Two crystal structures of Ce(IV) formate were determined. Both form a hexanuclear complex with a [Ce6(µ3-O)4(µ3-OH)4]12+ core in aqueous HNO3 / HCOOH solution. The pH titration with NaOH resulted in a structure with the composition [Ce6(µ3-O)4(µ3-OH)4(HCOO)10(NO3)2(H2O)3] (H2O)9.5, while the pH adjustment with NH3 resulted in [Ce6(µ3-O)4(µ3-OH)4(HCOO)10(NO3)4] (NO3)3(NH3)3(H2O)5. Furthermore, the crystal structure of Ce(III) formate, Ce(HCOO)3, was determined. The coordination polyhedron is a tricapped trigonal prism which is formed exclusively by nine HCOO- ligands. The hexanuclear Ce(IV) formate species from aqueous solution is widely preserved in the crystal structure, whereas the mononuclear solution species of Ce(III) formate undergoes a polymerization during the crystallization process.

Tetravalent actinides form strong complexes with carboxyl containing ligands. Such complexes play an important role in technological processes as well as biological and environmental systems. The aqueous chemistry of such complexes is therefore of wide interest. So far, most of the thermodynamic data of actinide(IV) carboxylates are estimated assuming mononuclear solution species (see for example [1]). We applied comprehensive spectroscopic studies (EXAFS, UV-Vis-NIR spectroscopy and X-ray diffraction) to estimate the complex structure of actinide(IV) carboxylates with different actinides (Th4+, U4+ and Np4+) and carboxylates (RCOO–; R = H, CH3, CHR’NH2; R’ = H, CH3, CH2SH) in aqueous solution and solid state [2-4]. These studies show clearly that in all of the investigated systems hexanuclear complexes appear, which become predominant with increasing metal and ligand concentration as well as increasing pH, and comprise finally often close to 100% of the species distribution. The aim of our studies was to investigate the complex structure, stability constants, and the mechanism of complex formation.

Herein, we present simple and rapid colorimetric and UV/VIS spectroscopic methods for detecting anionic arsenic (V) complexes in aqueous media. The methods exploit the aggregation of S-layer-functionalized spherical gold nanoparticles of sizes between 20 and 50 nm in the presence of arsenic species. The gold nanoparticles were functionalized with oligomers of the S-layer protein of Lysinibacillus sphaericus JG-A12. The aggregation of the nanoparticles results in a color change from burgundy-red for widely dispersed nanoparticles to blue for aggregated nanoparticles. A detailed signal analysis was achieved by measuring the shift of the particle plasmon resonance signal with UV/VIS spectroscopy. To further improve signal sensitivity, the influence of larger nanoparticles was tested. In the case of 50 nm gold nanoparticles, a concentration of the anionic arsenic (V) complex lower than 24 ppb was detectable.

Background
Assessment of dual time point (DTP) positron emission tomography was carried out with the aim of a quantitative determination of Km, the metabolic uptake rate of [18F]fluorodeoxyglucose as a measure of glucose consumption.

Methods
Starting from the Patlak equation, it is shown that Km?mt/ca0 + Vr/?a, where mt is the secant slope of the tissue response function between the dual time point measurements centered at t=t0. ca0=ca(t0) denotes arterial tracer concentration, Vr is an estimate of the Patlak intercept, and ?a is the time constant of the ca(t) decrease. We compared the theoretical predictions with the observed relation between Ks=mt/ca0 and km in a group of nine patients with liver metastases of colorectal cancer for which dynamic scans were available, and Km was derived from conventional Patlak analysis. derived from conventional Patlak analysis. Twenty- two lesion regions of interest (ROIs) were evaluated. ca(t) was determined from a three-dimensional ROI in the aorta. Furthermore, the correlation between Km and late standard uptake value (SUV) as well as retention index was investigated. Additionally, feasibility of the approach was demonstrated in a whole-body investigation.

Results
Patlak analysis yielded a mean Vr of Vr = 0.53?0.08 ml/ml. The patient averaged ?a was 99?23 min. Linear regression between Patlak-derived Km and DTP-derived Ks according to Ks = b ? Km + a yielded b = 0.98 ? 0.05 and a = -0.0054 ? 0.0013 ml/min/ml (r = 0.98) in full accordance with the theoretical predictions b = 1 and a ? -Vr=?a Ks exhibits better correlation with Km than late SUV and retention index, respectively. K(c)s = Ks + Vr=?a is proposed as a quantitative estimator of Km which is independent of patient weight, scan time, and scanner calibration.

Conclusion
Quantification of Km from dual time point measurements compatible with clinical routine is feasible. The proposed approach eliminates the issues of static SUV and conventional DTP imaging regarding influence of chosen scanning times and inter-study variability of the input function. Ks and K(c)s exhibit improved stability and better correlation with the true Km. These properties might prove especially relevant in the context of radiation treatment planning and therapy response control.

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper reviews the procedures and the problems during commissioning the new RF system.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper gives an overview on the activities and the problems during high power CW operation.

With the expansion of the radiation source ELBE, a centre for high power radiation sources is being built until 2014 at the Helmholtz Zentrum Dresden Rossendorf. One part of this program is to double the beam current of the ELBE LINAC. In January 2012 the 10 kW CW klystrons, used to operate the superconducting cavities of ELBE since 2001, had been replaced by a pair of 10 kW solid state amplifiers. The paper gives an overview on the activities around this project and the first experience with the new RF-system.

We report on pairs of diverging/converging spin vortices in Co/Rh/Ni81Fe19 trilayer disks. The lateral magnetization distribution of these effective spin merons is imaged directly by means of element-selective x-ray microscopy. By this method, both the divergence and circulation states of the individual layers are identified as antisymmetric. Reversal measurements on corresponding continuous films reveal that biquadratic interlayer exchange coupling is the origin for the formation of effective meron pairs. Furthermore, their three-dimensional magnetization structure is determined by micromagnetic simulations. Interestingly, the magnetic induction follows a kind of flux-closing torus. This toroidal topology enforces a symmetry break, which ties the core polarities to the divergence configuration.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper gives an overview on the activities and the problems during high power CW operation.

The study of Ni-Ti shape memory alloy films is of great technological interest for applications in the field of microengineering. They can work as sensors and actuators at the same time. However, there are still important issues unresolved like formation of film crystallographic orientation and its control. Films exhibiting the two-way shape memory effect are also required.
A two-magnetron sputter deposition chamber mounted into the six-circle diffractometer of the Rossendorf Beamline at the European Synchrotron Radiation Facility was used for the processing of Ni-Ti films. The in-situ x-ray diffraction studies enabled to identify the different steps of the structural evolution during film growth.
Deposition conditions leading to Ni-Ti films mainly containing grains with (100) or (110) planes of the B2 phase parallel to the film surface were successfully defined. This is an important achievement since texture has a strong influence on the extent of the strain recovery. The deposition of films with a “two-way” actuation (films with a combination of superelasticity and shape memory characteristics) was also achieved. It will allow the development of smaller devices since no consideration has to be paid to a resetting spring.

no abstract available

Flashing evaporation of water inside a vertical pipe under four different system pressures is investigated by mono-dispersed CFD simulations. Phase change is assumed to be caused only by thermal heat transfer. The available thermal energy decreases rapidly with the increase of pressure level. Under low-pressure conditions, the maximum steam volume fraction is over-predicted, while an overestimation is observed in high-pressure cases. The possible explanation for the deviation is that bubble growth during the evaporation is especially significant in low-pressure cases, which reduces the evaporation rate but is not considered in the simulation. Furthermore, as the system pressure increases the contribution of nucleation to the total steam generation rate becomes large, which is confirmed by the experimental data. In addition, the effect of pressure on the critical bubble diameter that succeeds in starting flashing as well as the nucleation mechanism is discussed.

The linear dispersion for electrons in graphene leads to a non-equidistant Landau-level (LL) spectrum. This enables one to investigate single Landau-level transitions by resonant pump-probe experiments. So far, however, only the quasi-continuum of high-index LL states has been studied in near-infrared pump-probe experiments. Here we report on terahertz pump-probe measurements at a fixed photon energy of 14 meV, where the free-electron laser FELBE at Dresden-Rossendorf served as radiation source. The magnetic field was varied between 0 T and 7 T. For these measurements we used a sample with 50 layers of graphene, which were epitaxially grown on the C-face of silicon carbide. While the interface layers are highly doped, the major part of the layers is quasi neutral with a Fermi energy in the range of ~10 meV.
At a magnetic field of 0.165 T the photon energy of 14 meV becomes resonant with the inter-LL transition LL-1(0) -> LL0(1). The amplitude of the pump-probe signal is increased by roughly a factor of 4 compared to zero field. Only the quasi neutral layers contribute to this signal, since the first LL is fully occupied for the interface layers with a higher doping. Surprisingly a decreased relaxation time is observed on resonance. We will discuss how the contribution of the LL-1 -> LL0 and LL0 -> LL1 and Auger-type processes lead to a unique relaxation scenario. At higher magnetic fields higher intraband LL transitions can be tuned into resonance (LLn -> LLn+1, n=1,2,3,…). The observed pump-probe signals then stem from these transitions in the interface layers, where the elevated Fermi energy ensures that the ground state LL is populated. With increasing magnetic field both amplitude and decay time constants vary non-monotonically. In the magnetic field region around 3 T negative pump-probe signals occur. The main features observed in the experiments are explained by a model for the electron temperature after optical excitation, which describes the absorption in the layers via the Kubo formalism and takes into account the doping level of the interface layers. The doping levels agree well with values previously obtained from pump-probe experiments without magnetic field.

In this work we study the THz transmission of a 40 nm wide undoped In0.1Ga0.9As quantum well (QW) under optical excitation. Carriers are photoexcited by a near-infrared (NIR) fs pulse and probed in the frequency range from 0.1 to 3 THz by electro-optic sampling using the modified setup of Ref. [1]. The THz pulse is focused on a side facet of the QW sample such that the THz electric field is mostly polarized perpendicular to the QW layer. Fig. 1a depicts the THz field transients for modulated (signal) and un-modulated (reference) NIR excitation. The presence of the carriers which were photoinjected several ps prior to the THz pulse creates a large amount of THz signatures in the QW. Our present goal is to disentangle the various possible contributions to the THz signal: electron intersubband, heavy-hole intersubband, 1s-2p intraexciton and free-carrier absorption. In addition we search for a Fano-like behavior, similar as has been observed in narrower QWs in the mid infrared [2], which is supposed to arise from the interplay between the intersubband absorption and the purely reactive ponderomotive contribution. The different phase of the associated dielectric functions results in a (non-quantum like) interference between these two polarizations, which is only visible in the differential transmission but not in the absorption. We will also report experiments where we use wavelength tuning of the near-infrared pulse using an optical parametric amplifier in order to selectively pump optically either into the barrier or into the QW. Polarization resolved measurements are underway which should help us to reveal the various contributions.
[1] M. Wagner et. al. , Appl. Phys. Lett. 99, 131109 (2011).
[2] D. Golde, M. Wagner et. al., PRL 102, 127403 (2009).

Presentation of my scientific CV, laser-electron theory at HZDR and the work on PIConGPU.

Presentation of recent feature enhancements and physical Validations of PIConGPU. We presented laser dispersion test, radiation tests and thermal plasma tests, added new numerical shemes for the PIC cycle and performed HPC simulations for the recent laser-electron experiment at draco, performed by A. Irman et al.

Contribution to the Annual Report 2012 of EPP/IPFN at Instituto Superior Técnico (Lisboa).

The transverse spin correlations Ax,x and Ay,y have been measured in the ~d~p ! pspec{pp}sπ−reaction at COSY-ANKE at 353 MeV per nucleon. Here {pp}s denotes a proton-proton pair with low excitation energy, which is dominantly in the 1S0 state. By measuring three protons in the final state it was possible to extract events where there was a spectator proton pspec so that the reaction could be interpreted in terms of quasi-free ~n ~p ! {pp}sπ−. The proton analyzing power in this reaction was also deduced from this data set by averaging over the polarization of the deuteron beam. The values of A^p _y were shown to be consistent with a refined analysis of our earlier results obtained with a polarized proton incident on a deuterium target. Taking these data in combination with our earlier measurements of the differential cross sections and analyzing powers in the ~pp ! {pp}s π0 reaction, a more robust partial wave decomposition was achieved. Three different acceptable solutions were found and the only way of resolving this ambiguity without further theoretical input would be through a measurement of the mixed spin-correlation parameter Ax,z.

Final talk about the results of the cooperation/internship at Instituto Superior Técnico (IST) in 2012/13.
A new method for charged beam loading in particle-in-cell simulations was presented. Furthermore, side-topics like the creation of a Raspberry Pi (ARM) cluster, the development of a dependency analyser for fortran modules for parallel builds, a GPU vs CPU benchmark, the development of a transversal resolution criteria for gaussian laser beams and a Thrust-Fortran binding were presented.

PIConGPU is a highly-scalable implementation of the fully relativistic electromagnetic particle-in-cell algorithm for GPGPUs. It allows for fast simulations of laser plasma interaction and astrophysical plasmas.
We present several physics validation results, allowing reliable checks during development stages of the code. Furthermore, we show applications in astrophysical scenarios and in laser wakefield acceleration experiments for next generation electron accelerators.

Dissipative solitons have been reported in a wide range of nonlinear systems, but the observation of their magnetic analog has been experimentally challenging. Using spin transfer torque underneath a nanocontact on a magnetic thin film with perpendicular magnetic anisotropy (PMA), we have observed the generation of dissipative magnetic droplet solitons and report on their rich dynamical properties. Micromagnetic simulations identify a wide range of automodulation frequencies, including droplet oscillatory motion, droplet "spinning," and droplet "breather" states. The droplet can be controlled by using both current and magnetic fields and is expected to have applications in spintronics, magnonics, and PMA-based domain-wall devices.

We introduce a parametric family for random convex polytopes in Rd which allows for an easy generation of samples for further use, e. g., as random particles in materials modelling and simulation. The basic idea consists in weighting the Poisson cell, which is the typical cell of the stationary and isotropic Poisson hyperplane tessellation, by suitable geometric characteristics. Since this approach results in an exponential family, parameters can be efficiently estimated by maximum likelihood. This work has been motivated by the desire for a flexible model for random convex particles as can be found in many composite materials such as concrete or refractory castables.

With the observation of superconductivity at ambient pressure conditions in B doped Si in 2006 [1] and Ga doped Ge [2] the group-IV semiconductors become of interest for future information processing technologies like quantum computing.
To achieve the high doping levels needed for superconductivity non-equilibrium doping techniques like gas immersion laser doping or ion implantation and short term annealing are needed. Only the latter one is fully compatible to standard microelectronic technology. In a new approach we implanted a Ga concentration up to 11 at.% through a 30 nm SiO₂ cover layer into commercial Si and Ge wafers [3-6]. During annealing a thin superconducting Ga-rich nanolayer is formed at the SiO₂/semiconductor interface. These layers show promising superconducting properties (T_C = 7 K, B_C < 8 T, j_C < 50 kA/cm2).
Detailed microstructural investigations by means of XTEM and RBS/C will be discussed. Recent results show the adjustability of the superconducting properties. We are able to produce superconducting microstructures having a width of 3 µm and used the FIB to implement a Josephson junction as key element for a prospective SQUID.
[1] E. Bustarret et al., Nature 444 (2006) 465
[2] T. Herrmannsdörfer et al., Phys, Rev. Lett. 102 (2009) 217003
[3] R. Skrotzki et al., Appl. Phys. Lett. 97 (2010) 192505
[4] J. Fiedler et al., Phys. Rev. B 83 (2011) 214504
[5] J. Fiedler et al., Phys. Rev. B 85 (2012) 134530
[6] V. Heera et al., Appl. Phys. Lett. 100 (2012) 262602

The former salt mine (1908-1964) Asse II, Germany is a final disposal site of radioactive waste. It is composed of salt rocks, which are approximately 250 million years old. A number of salt sumps exist in the Asse II, which were so far not microbiologically characterized. In this study, cultivation-independent methods, e.g. pyrosequencing, were applied to identify the microbial diversity in these unique salt sump habitats.
In this study, a total of 3.168 sequences, divided in 314 operational taxonomic units (OTUs), representing bacterial and archaeal groups from the underground Asse II salt mine. The class halobacteria (Euryarchaeota) predominates the archaeal community, representing 99.5% of all sequences. The least abundant sequences were represented by Thermoprotei (Crenarchaeota) and Methanobacteria (Euryarchaeota).
In addition, halophilic bacteria have been detected in the salt sumps of the underground Asse II mine. A total of 8 phyla of bacteria were identified by 16S rRNA sequence analyzes. The dominating phylum are Firmicutes (e.g. Bacilli, Halocella, Filifactor, Veillonella) with ~51% of all detected bacterial sequences, followed by Proteobacteria (Marinobacter, Hyphomicrobium, Methylophilus, Pseudomonas, Sphingomonas) with ~19%.
This study identified for the first time extreme halophilic bacteria and archaea in the underground salt sumps of the Asse II environment. For generating a final disposal site, not only geological, chemical or physical, but also microbiological aspects are important to consider.

All-optical switching (AOS) in ferrimagnetic Fe100−x Tbx alloys is presented. AOS is witnessed below, above, and in samples without a magnetic compensation point. It is found that AOS is associated with laser heating up to the Curie temperature and intimately linked to a low remanent sample magnetization. Above a threshold magnetization of 220 emu cm−3 helicity dependent AOS is replaced by pure thermal demagnetization.

In the coming years supercomputers will have millions of compute cores.
It is estimated that the computing power will grow by a factor of 1000 in the coming years while the memory will only grow by a factor of 10.
This means that at optimum codes can be 100 times faster than before.
I will show that such codes exist today and both allow and require online visualization and interaction with the user.
Based on the example of particle-mesh methods I will present the most important techniques on how to write optimum codes.

The release of engineered titanium dioxide nanoparticles in the environment is nowadays continuously increasing due to their wide range of industrial applications. Their potential toxicity effects became of major concern and several assessment studies in natural waters were already undertaken. However, no consensus arised about the environmental factors influencing their hazardous impact, but rather contrary conclusions were drawn. In this study, the acute toxicity of commercial TiO2 nanoparticles suspensions at different concentrations on microcrustacean (Daphnia magna), marine rotifers (Brachionus plicatilis) and marine microalgae (Phaeodactylum tricornutum) under environmental conditions, in synthetic fresh and marine water, was investigated. Factors driving TiO2 adverse effects on aquatic environment, such as allotropic form, primary particle size, surface area, particle concentration and agglomerate size were studied. A thorough characterization of both surface and bulk properties of nano-sized TiO2 particles was therefore performed. Our results showed that Daphnia magna test is the most sensitive test for assessing toxicity of TiO2 samples on aquatic organisms. For anatase samples, toxicity towards aquatic organisms depends (i) on the primary particle size and the extent of agglomeration (mass median diameter d50), and consequently on surface reactivity (total surface site concentration, specific surface area, pHIEP) (ii) on the presence of rutile impurities in the sample.
Toxicity results of rutile and anatase samples of comparable primary particle size (sub micrometric range) are of same order of magnitude and remained less toxic than nanometric particles. Rutile agglomeration was found to be higher than anatase agglomeration, toxicity results obtained for rutile could be attribute to the shape of particles, or it could be due to the presence of BaTiO3 impurities.
This work emphasized the importance of studying the effects of different bulk and surface parameters of engineered TiO2 nanoparticles to understand their reactivity towards micro-organisms under environmental conditions.

Intraband excitation of optically injected carriers using strong mid-infrared or THz pulses provides interesting opportunities to study carrier and exciton dynamics in semiconductor quantum wells (QW). In particular, owing to the odd parity of the dipole operator, such intraband excitation transfers excitons located in radiative states into dark (or interband-forbidden) states as long as the symmetry of the QW ensures parity conservation. This property yields spectroscopic access to specific dark states, giving rise to resonant enhancement of intraband absorption as well as suppression of the photoluminescence (PL), and allows us to investigate associated dynamical processes.
We will report on time-resolved PL studies, where we investigate the dynamics of excitons and electron-hole plasma subsequent to pulsed irradiation using the free-electron laser (FEL) at the Helmholtz-Zentrum Dresden-Rossendorf. The FEL is tuned into resonance with, respectively, intraexcitonic and intersubband transitions. Specifically, Figs. 1(a)-(b) demonstrate the effect of FEL excitation of radiative excitons in resonance with the 1s-2p transition, located at 9 meV for 8.2 nm wide high-quality QWs (sample 1). Besides quenching and recovery of the 1s PL, the salient feature in Fig. 1(b) is the appearance of PL originating from the 2s exciton. As direct excitation from 1s into 2s is dipole forbidden, the latter has to be the consequence of rapid scattering from the 2p into the 2s state, which nicely confirms earlier theoretical predictions. This 2s PL is specific for resonant 1s-2p excitation and just seen in high-quality quantum wells. Figs. 1(c) and (d) show PL transients for FEL excitation at 173 meV, in resonance with the electron intersubband transition for 6 nm wide GaAs QWs (sample 2). Typically, the PL recovery after the FEL pulse obeys the same time constant as the initial PL formation after NIR excitation, and its value after recovery exceeds the reference value since the population transferred into nonradiative states eventually returns into the radiative ones, such that the time-integrated PL emission is conserved.

After the German reunification the Wismut GmbH, formerly the 3rd largest U producer of the world, started to remediate the legacies of their U mining activities. As part of the remediation strategy the pit body was flooded to induce reductive processes. Although flooding of the mines Pöhla and Schlema-Alberoda was already finished about ten years ago, the mine water still contains elevated concentrations of toxic metals such as U, As and Ra. Thus, expensive and long-lasting monitoring and waste water treatment is required. Since microorganisms can influence the toxicity of metals directly or indirectly, one alternative approach is to use them for bioremediation. Here, the diversity of the indigenous microbial community of the mine water from Pöhla and Schlema-Alberoda is reported. Bacteria as well as Archaea were analyzed by state-of-the-art pyrosequencing of the 16S rRNA gene. Mine water samples were either filtrated or harvested from a flow cell. For the filtrated Pöhla mine water, the Pöhla flow cell, the filtrated Schlema mine water, and the Schlema flow cell 485, 697, 325 and 527 sequences, respectively, were divided into 98, 189, 188 and 89 operational taxonomical units (OTUs), respectively, belonging mainly to Bacteria. The bacterial sequences from the Pöhla mine were classified into Proteobacteria, Verrumicrobia, Bacteriodetes, WS3, Chloroflexi, Firmicutes, Acidobacteria, SR1, Actinobacteria, Spirochaetes and OD1. For the Schlema mine Proteobacteria, Acidobacteria, WS3, Bacteriodetes, Chloroflexi, SR1, Chlorobi, TM7 and Acinobacteria were found. The dominant bacterial phylum in all samples are the Proteobacteria. Higher bacterial diversities were observed in flow cells in comparison with filtrated waters. A dataset of 15786, 17872, 11404, 7780 sequences revealed 639, 643, 769 and 455 OTUs, respectively, mainly for Archaea of the filtrated Pöhla mine water, the Pöhla flow cell, the filtrated Schlema mine water and the Schlema flow cell, respectively. The archaeal sequences of the Pöhla as well as the Schlema mine water belong to the class of Methanobacteria, Thermoprotei, Methanomicrobia, Thermoplasmata and Halobacteria.

We use terahertz pulses to induce resonant transitions between the eigenstates of optically generated exciton populations in a high-quality semiconductor quantum well sample. Monitoring the excitonic photoluminescence, we observe transient quenching of the 1s exciton emission, which we attribute to the terahertz-induced 1s-to-2p excitation. Simultaneously, a pronounced enhancement of the 2s exciton emission is observed, despite the 1s-to-2s transition being dipole forbidden. A microscopic many-body theory explains the experimental observations as a Coulomb-scattering mixing of the 2s and 2p states, yielding an effective terahertz transition between the 1s and 2s populations.

In this comparative study, the surface speciation of uranium(VI) on ferrihydrite (Fh) and maghemite (Mh) were investigated by vibrational spectroscopy. The experimental setup allows the monitoring of the surface processes at the water-solid interface in real time with a time resolution in the subminute time range. The performance of the experiments under inert gas atmosphere and under ambient conditions provides further insight into the molecular events of the binary and ternary sorption systems, respectively.
The spectra clearly demonstrate a characteristic surface speciation in dependence of the solid phase. On Fh, the formation of ternary inner sphere complexes are observed as it was derived earlier [1]. In addtion, the time-resolved spectra reveal the change of the surface speciation of atmospherically derived carbonate upon U(VI) sorption [2].
From the sorption experiments on Mh, outer sphere complexation of the uranyl ion can be derived. In ambient atmosphere, contributions of carbonate ions to the U(VI) surface speciation on Mh can not be ruled out.

[1] Ulrich et al. (2006) Geochim. Cosmochim. Acta 70, 5469-5487. [2] Foerstendorf et al. (2012) J. Colloid Interface Sci. 377, 299-306.

In the present study we investigated the reduction of SeO32− by Azospirillum brasilense. The formation of fairly soluble Se(0) nano-particles during this process might be of interest for both bioremediation of Se-contaminated sites and for nanobiotechnology. After A.brasilense being exposed to Se(IV), the bacterial growth continued subsequent to a prolonged lag-phase. After a cultivation time of 3 days, a clearly reddish staining of the sample was observed and a bright red precipitate occurred, indicating the formation of Se(0) nano-particles. The SEM-EDX spectra derived from the nano-spheres indicated that they mainly consist of selenium. In addition, only 10 % of the initial Se(IV) concentrations was recoverd in culture media by means of HG-AAS, indicating a Se(IV) removal from the media. The isolated and resuspended Se(0) nanoparticles showed a long time stability of some hours, which is sufficient for the PCS and the zeta potential measurements. In contrast, Se(0) chemically formed by reduction with hydroxylamine solution produced amorphous aggregates with a rapid sedimentation behavior. The PCS measurement and the SEM imaging of the Se(0) particles showed a particle size distribution between 100 and 300 nm with an averaged particle diameter of 200 nm. The isoelectric point of Se(0) particles was found at pH 2.8 ± 0.2. The preference of forming Se(0) particles with a negative charge agree very well with the literature [1].

[1] Dhanjal & Cameotra (2010) Microb. Cell Fact. 9,1-11.

One major process controlling the mobility and bioavailability of selenium, a long-lived fission product found in nuclear waste, is the adsorption onto mineral surfaces of both the engineered and geological barrier. In this context, it is important to understand to what extent this sorption is influenced particularly by characteristic parameters as expected in deep underground repositories for high level and long-lived radioactive waste. These parameters include inter alia the presence of different background salts which are important with regard to salt domes as potential repositories.
In the present study, a combination of macroscopic sorption experiments, electrophoretic mobility and in-situ ATR FT-IR spectroscopy measurements was used to study the interaction of selenate with aged γ-Al2O3 in the presence of NaCl and MgCl2. From in-situ ATR FT-IR spectra, a change in the symmetry of the aqueous tetrahedral selenate anion can be derived evidencing the formation of a surface complex on γ-Al2O3. From batch experiments, we observe a dependence of selenate sorption on the ionic strength and composition of the electrolyte. Additionally, the sorption generally decreases with increasing pH. However, in the presence of 0.1 M MgCl2, the sorption increased again at a pH above 9.5.
The isoelectric point (pHIEP) of γ-Al2O3 is located at pH 9.6 for low NaCl background electrolyte concentration (I = 0.1 M). The increase of ionic strength (up to I = 1 M) results in a decrease of the zeta potential for both the acidic and alkaline pH range. However, in the alkaline range the decrease of the zeta potential is more pronounced. Additionally, we observe that the pHIEP is shifted to more alkaline values and finally no charge reversal is observed. In the presence 0.1 M MgCl2, the surface charge of γ-Al2O3 is positive throughout the studied pH range (3-11). Above pH 10, a sharp potential decrease occurs due to Mg(OH)2 precipitation. The impact of the varied parameters on the sorption of selenate in the alkaline pH range will be verified in detail.

The retention behavior of the crystalline rock diorite from the Äspö Hard Rock Laboratory (HRL, Sweden) towards the redox-sensitive actinides U and Np was studied by means of batch sorption experiments. The influence of various parameters, such as grain size (0.063 – 0.2 mm, 0.5 – 1 mm, 1 – 2 mm), temperature (25 and 10°C), atmosphere and sorption time (5 to 108 days) was studied using a synthetic Äspö groundwater (pH 7.8, I = 0.178 M) as background electrolyte. For U(VI), sorption isotherms were recorded (5x10⁻⁹ M to 7x10⁻⁵ M). Distribution coefficients, K_d values, were determined.

There is no abstract.

The free-electron laser (FEL) facility FELBE in Dresden provides unique opportunities to advance our knowledge on the interaction of intense mid-infrared and terahertz fields with materials and devices. Its nearly transform-limited ps pulses, which can also be combined with synchronous ps or fs pulses from near-infared tabletop lasers, represent a versatile radiation source for novel experiments, which is also available to external users. This talk reviews some of our recent experimental studies, which are also representative for advanced measurement techniques at FELBE.
In high-quality semiconductor quantum wells, time-resolved photoluminescence allows us to investigate the dynamics of excitons, i.e. two-dimensional, hydrogen-like electron-hole quasiatoms. In particular, applying time-delayed FEL pulses tuned to the intra-excitonic 1s-2p transition (at 9 meV for an 8 nm wide GaAs/AlGaAs quantum well), we have studied the population transfer between the 2p and 2s exciton states. Moreover, strong terahertz pumping in resonance with the 1s-2p transition results in a characteristic splitting (Rabi splitting) of the 1s exciton state, which is a manifestation of the intra-excitonic Autler-Townes effect [1].
In semiconductor quantum dots, resonant excitation between s, p and d sublevels in these zero-dimensional atom-like nanostructures is shown to produce an absorption contrast in aperture-less scattering scanning near-field optical microscopy (s-SNOM). This effect allows us to obtain functional s-SNOM images with deep sub-wavelength resolution, where far-infrared absorption by single electrons produces sufficient contrast to map individual quantum dots [2].
In graphene, FEL-based pump-probe spectroscopy has shown evidence of different relaxation times for excitation energies above and below those of the optical phonons, as well as a transition from induced transmission (bleaching) to induced absorption if the photon energy becomes smaller than twice the Fermi energy [3]. In particular, the latter observation is indicative for interesting potential applications of this two-dimensional semiconductor material, e.g. as an electro-optical modulator.
[1] J. Wagner et al., Phys. Rev. Lett. 105, 167401 (2010)
[2] R. Jacob et al., Nano Lett. 12, 4336–4340 (2012))
[3] S. Winnerl et al., Phys. Rev. Lett. 107, 237401 (2011)

There is no abstract.

High conversion Light Water Reactor concepts typically rely on heterogeneous core configuration, where fissile zones are interspersed with fertile blanket zones in order to achieve high conversion ratio. Such a heterogeneous structure renders the modeling of these cores impossible using conventional reactor analysis methods. It was recently suggested to overcome such difficulties, in particular, for the case of axially heterogeneous reduced moderation BWRs, by introducing additional set of discontinuity factors in the axial direction at the interfaces between fissile and fertile fuel assembly zones. However, none of the existing nodal diffusion core simulators have the capability of accounting for discontinuity of homogeneous nodal fluxes in the axial direction since the fuel composition of conventional LWRs is much more axially uniform. In this work, we modified nodal diffusion code DYN3D by introducing such capability. The new version of the code was tested on a series of reduced moderation BWR cases with Th-U233 and U-Pu-TRU fuel. The library of few-group homogenized cross sections and the data required for calculation of discontinuity factors were generated using Monte Carlo transport code Serpent. The results obtained with the modified version of DYN3D were compared with the reference Monte Carlo solutions and were found to be in a good agreement. The current analysis demonstrated that high conversion LWRs can in principle be modeled using existing nodal diffusion core simulators.

An innovative light water reactor constructed as a multitude of modular, horizontal fuel channels has been proposed. The basic novelty of the proposed design is an implementation of the “breed & burn” mode of operation by a dynamic variation of the moderator content in the core. This paper describes the novel reactor core design and explores the physical principles underlying its operation. Initially, a single fuel channel assembly was analyzed in order to evaluate the impact of the moderator variation on the reactivity and “breed & burn” processes. At the second stage, a full core model was analyzed, demonstrating a possibility of a realistic fuel management scheme with on-power moderator addition. The BGCore Monte-Carlo based depletion code was used for the analyses. It has been shown that the proposed design has a potential to increase the fuel utilization, attain negative reactivity coefficients and reduce the excess core reactivity during the power operation. The physical observations, presented and discussed in this paper, provide an interesting research lines for future investigation and continuous design developments.

The compact neutron-time-of-flight facility nELBE at the superconducting electron accelerator ELBE of Helmholtz-Zentrum Dresden-Rossendorf is currently being rebuilt. As the neutron radiator consists of a liquid-lead circuit no moderated neutrons are produced and also the background from capture gamma-rays is very small. The useful neutron spectrum extends from some tens of keV to about 10 MeV. nELBE is intended to deliver cross section data of fast neutron nuclear interactions e.g. for the transmutation of nuclear waste and an improvement of neutron physical simulations of innovative nuclear systems. The new experimental hall will allow measurements of angular distributions in neutron scattering. Inelastic neutron scattering, e.g. on 56Fe, has been studied with a double time-of-flight setup and with photon detectors to measure the gamma-rays produced in the process. The neutron total cross sections of Au and Ta were determined in a transmission experiment.

The world’s first permanent nuclear-waste repository for high-level waste (HLW) will be the underground rock characterization facility tunnel ONKALO, situated near the nuclear power plants of Olkiluoto, approximately 300 km northwest of Helsinki (Finland). Geological mapping showed that the bedrock of the tunnel is mainly composed of veined gneisses with a migmatic appearance, which are interspersed by numerous fractures. Massive 5–10-mm thick biofilms (microbial communities) are observed attached to the tunnel walls where groundwater is seeping from bedrock fractures feeding the biofilm. Groundwater and biofilm samples were taken during the EURATOM collaborative project ReCosy for laboratory experiments in flow cells, where uranium(VI) was added to the circulating groundwater with a final uranium concentration (4.25×10–5 M), which was expected from a damaged and leaking waste canister in the far-field of a nuclear-waste repository. The aim of our studies was to simulate the fate and behaviour of uranium(VI) in the presence of microorganisms using different methods to find evidence of the possibility of uranium retention.

In our experiments, aqueous uranium percolated the biofilm and induced interaction between biofilm microorganisms and uranium(VI), forming an intracellular U-phosphate mineral similar to autunite (Ca[UO2]2[PO4]2 • 2-6H2O or meta-autunite Ca[UO2]2[PO4]2 • 10-12H2O) as determined by means of EF-TEM/EELS. The potential toxicity of uranyl was consequently avoided by the uranium forming these strong complexes with phosphate in the cytoplasm of these microorganisms. Inorganic phosphate (H2PO4–) was released from the cellular polyphosphate as a cells’ response to the heavy metal stress. In contrast, aqueous uranium carbonate species, likely calcium uranyl carbonates species (Ca2UO2[CO3]3), were formed using the large available amount of carbonate in the uranium-contaminated circulating groundwater. The results of the laser-induced fluorescence spectroscopy studies performed at 283 K are in excellent agreement with the thermodynamic calculations of the theoretical predominance fields of the uranium species formed in the uranium-contaminated circulating groundwater. These complexes consequently influence the speciation of uranium, contributing to the transport and migration of uranium(VI).

Our studies aimed to improve our understanding of the mechanisms by which biofilms respond to the exposure to radionuclide with respect to safety assessments in the far-field of nuclear-waste repositories. In this environment, microorganisms must be considered, along with minerals, as an important factor influencing radionuclide transport.

With PIConGPU, new physics phenomena previously not accessible within laser plasma simulations can be studied, which will help us optimize laser-driven radiation sources. Presents results on laser wakefield acceleration of electrons simulated on the Oakridge TITAN system and discuss in detail which techniques help us to get the most out of these clusters. Finally showing how to add fault-tolerance and load-balancing to a large hybridh CPU-GPU code such as PIConGPU to achieve optimum performance.

We present the algorithmic building blocks of PIConGPU, one of the fastest implementations of the particle-in-cell algortihm on GPU clusters. PIConGPU is a highly-scalable, 3D3V electromagnetic PIC code that is used in laser plasma and astrophysical plasma simulations.

To allow simulation of nanosecond scale plasma processes, we are developing a 3D fully relativistic fluid code with LTE (local thermal equilibrium) closure. This code is intended to be able to take output from PIC simulations as its initial state, to allow self-consistent simulation of processes acting over multiple time and density scales. In this code, both electrons and ions are treated as inertial fluids. Local fluid pressure is tied to the energy density using the Maxwell-Jüttner distribution, allowing investigation of the effect of local temperatures on, for example, the expanding sheath in TNSA (target normal sheath acceleration) experiments.

Plasma heating and ionization are important processes during the interaction of high power ultra-short laser pulses with solid density targets. In order to understand the relevant physics, particle-in-cell simulations including collisions and ionization were run to study ion heating dynamics in buried layer targets illuminated by high-intensity, ultra-short laser pulses. Our results show that bulk ions can be heated to above 1keV temperature. When studying the ionization dynamics strong filaments have been observed which depend on preplasma on the target front side, laser pulse duration and intensity. In order to study the evolution of ionization and ion bulk heating in experiment, ultra-bright X-ray free electron lasers - such as the European XFEL - are a very promising and strong tool to resolve the spatial and temporal scales of these processes inside the solid target.

High-precision measurements of the hyperfine splitting values on Li- and H-like bismuth ions, combined with precise atomic structure calculations allow us to test QED-effects in the regime of the strongest magnetic fields that are available in the laboratory. Performing laser spectroscopy at the experimental storage ring (ESR) at GSI Darmstadt, we have now succeeded in measuring the hyperfine splitting in Li-like bismuth. Probing this transition has not been easy because of its extremely low fluorescence rate. Details about this challenging experiment will be given and the achieved experimental accuracy will be presented.

We present new results on broadband laser cooling of stored relativistic C3+ ion beams at the ESR in Darmstadt. For the first time we could show laser cooling of bunched relativistic ion beams using a UV-laser which could scan over a very large range and thus cool all the ions in the ‘bucket’. This scheme is much more versatile than a previous scheme, where the bunching frequency was scanned relative to a fixed laser frequency. We have also demonstrated that this cooling scheme works without pre-electron cooling, which is a prerequisite for its general application to future storage rings and synchrotrons, such as the HESR and the SIS100 at FAIR. We also present results from in vacuo VUV-fluorescence detectors, which have proven to be very effective.

We present new results on laser cooling of relativistic C3+ ion beams at the Experimental Storage Ring at GSI. For the first time we could show laser cooling of bunched relativistic ion beams using fast scanning of the frequency of the cooling laser over a range larger than the momentum acceptance of the bucket. Unlike previously employed cooling schemes where the bucket frequency was scanned relatively to a fixed laser frequency, scanning of the laser frequency can be readily applied to future high energy storage rings such as HESR or SIS 100 at FAIR.

PIConGPU can handle large-scale simulations of laser plasma and astrophysical plasma dynamics on GPU clusters with thousands of GPUs. High data throughput allows to conduct large parameter surveys but makes it necessary to rethink data analysis and look for new ways of analyzing large simulation data sets. The speedup seen on GPUs enables scientists to add physical effects to their code that up until recently have been too computationally demanding. We present recent results obtained with PIConGPU, discuss scaling behaviour, the most important building blocks of the code and new physics modules recently added. In addition we give an outlook on data analysis, resiliance and load balancing with PIConGPU.

Aim:

Nicotinic α4β2* acetylcholine receptors (nAChR) are an important target for diagnostic neuroimaging because of their involvement in Alzheimer's disease, Parkinson's disease, tobacco and alcohol addiction. 2-[¹⁸F]FA-85380 (2-FA) has been used extensively for PET imaging of α4β2* receptors but is limited as biomarker by its unfavourable slow kinetic. The newly developed radiotracer (-)-[¹⁸F]-Flubatine (Flubatine) shows a significantly improved brain uptake, receptor affinity and selectivity (1). Here we estimated the compartmental parameters of both tracers by full kinetic modeling and compared them.

Materials and methods:

After intravenous administration of ~370 MBq radiotracer PET brain imaging was performed in 20 healthy controls with Flubatine (age 70.6±4.6, scan duration 90 min) and in 7 healthy controls with 2-FA (age 60.7±9.0, scan duration 420 min) using an ECAT EXACT HR+ system. PET frames were motion corrected with SPM2 and kinetic modeling using a 1-tissue compartment model (1TCM) with arterial input-function was applied to the volume of interest (VOI) based tissue time-activity curves (TACs) generated for 29 brain regions (anatomically defined via MRI co-registration). The model-based receptor parameter used was the total distribution volume V_T (ml/cm³), tracer uptake was measured by K₁ (ml/cm³/min) and tracer tissue clearance by k₂ (1/min).

Results:

For both tracers TACs of all 29 brain regions could be described appropriately with the 1TCM and all kinetic parameters could be reliably estimated from the PET data. Regional V_T increased as expected with regional nAChR density. Parameters of Flubatine in characteristic regions with very low, medium and high receptor density were: Corpus callosum (K₁= 0.18±0.04, k₂= 0.032±0.004, V_T= 5.68±1.01), Frontal cortex (K₁= 0.37±0.04, k₂= 0.040±0.003, V_T= 9.18±0.59), Thalamus (K₁= 0.48±0.06, k₂= 0.020±0.003, V_T= 25.03±3.33). The respective parameters of 2-FA were: Corpus callosum (K₁= 0.063±0.009, k₂= 0.014±0.003, V_T= 4.45±0.65), Frontal cortex (K₁= 0.099±0.013, k₂= 0.018±0.001, V_T= 5.42±0.56), Thalamus (K₁= 0.13±0.019, k₂= 0.010±0.001, V_T= 13.06±2.62).

Conclusions:

Flubatine is superior to 2-FA in tracer uptake velocity (characterized by K₁), velocity of washout (characterized by k₂) and in the amount of measured specific binding (characterized by V_T-target - V_T-reference). It shows a threefold higher uptake rate constant K₁ and a twofold higher washout rate constant k₂, providing the rational for much shorter scan durations in case of Flubatine. These results are in good agreement with our former findings in an animal (pig) model (1).

Reference:

1. P. Brust, ..O. Sabri: In vivo measurement of nicotinic acetylcholine receptors with [¹⁸F]Norchloro-Fluoro-Homoepibatidine (Flubatine). Synapse 2008;62:205-218.

We present recent results on TNSA, simulations and laser cooling of ion beams

Ziel/Aim:

Our aim was to port our previously developed high resolution 3D list-mode image reconstruction for the HR+ PET to the Philips Ingenuity TF PET/MR system. Porting to a different scanner usually requires a major rewrite to account for system specific aspects. Instead, a general interface was designed and implemented in our reconstruction to allow simultaneous support of multiple scanners and to facilitate future adoption to further scanner types. We report on application of this strategy for implementing our reconstruction on the Philips PET/MR.

Methodik/Methods:

We implemented a generalized interface using abstract classes which completely removes scanner dependency from the reconstruction algorithm and allows runtime switching between scanners. The reconstruction obtains system specific information
such as geometry parameters and data formats directly via an abstract interface using internal formats. The port to the Philips PET/MR was performed accordingly and evaluated: i) quantitative accuracy and spatial resolution in phantoms, ii) visual evaluation of patient studies, iii) runtime performance evaluation.

Ergebnisse/Results:

The use of an abstract interface influences the runtime performance of the reconstruction only minimal. The ported reconstruction shows substantial improvements in comparison to the vendor provided software. In phantoms we obtain improved resolution and a high level of quantitative accuracy. Visual inspection of phantom and patient data reveals an improved level of detail rendering.

Schlussfolgerungen/Conclusions:

The implementation of an abstract interface simplifies porting of the software to other scanners. For the Philips PET/MR we observed improved resolution and overall image quality compared to the vendor provided software. Support of Time-of-Flight information is currently implemented and already shows further improvements of image quality at reduced reconstruction times.

Ziel/Aim:

Members of the Eph receptor tyrosine kinase family play an essential role in the pathogenesis of cancer and, therefore, are promising candidates for molecular imaging purposes, e.g. by PET. In this regard, radiochemical access to 11C-radiotracers derived from potent inhibitors (IC₅₀ = 1.3 nM, calcd. logP = 3.42) targeting EphB4 kinase domain and bearing the indazolylpyrazole structural motif was developed.

Methodik/Methods:

The evaluation of a protecting group strategy based on the ethoxyethyl moiety (EOE) was necessary for the regioselective labeling with [¹¹C]CH₃I due to three secondary amino groups of the precursor. The labeling was accomplished in a remotely controlled synthesis module in three steps. The first step involved the preparation of [¹¹C]CH₃I from [¹¹C]CH₄, the second step comprehended the radiolabeling of the protected precursor and the final step included the cleavage of the protecting group.

Ergebnisse/Results:

The synthesis of the reference as well as the precursor was done starting from EOE protected indazole. Subsequent reaction with 2,4-diochloropyrimidine give the first substructure. For the preparation of the precursor, the first substructure was treated with 3,5-di(morpholino)aniline under Buchwald-Hartwig conditions. For the preparation of the reference, the first substructure was first methylated and then treated with 3,5-di(morpholino)aniline. The radiolabeling was done starting with ~ 1-1.5 GBq [¹¹C]CH₃I under basic conditions. After 2 min reaction time 1 M HCl was added and the mixture was maintained for 2 min. Approx. 200 MBq of the desired radiotracer could be obtained within 20 min after EOB (30-35% d.c. yield based on [¹¹C]CH₄).

Schlussfolgerungen/Conclusions:

The two-step radiolabeling of a novel indazolylpyrazole derivative with [¹¹C]CH₃I was successfully demonstrated. First stability tests showed beneficial behaviour ex vivo. Further biological studies for an application as radiotracer for functional tumor imaging are ongoing.

Literatur/References:

Mamat C, Mosch B et al. (2012) ChemMedChem 7:1991-2003.

Ziel/Aim:

The synthesis of fluorine-18 labeled peptides with high affinity towards the EphB2 receptor and the evaluation as radiotracers for PET was described. This receptor is known to be overexpressed in various types of cancer. Thus, a peptide was applied with high affinity to the EphB2 receptor which is strongly constrained of the amino acid key sequence SNEW. Two novel bifunctional and bioorthogonal building blocks were evaluated. The labeling of the peptides was done using the Huisgen click approach.

Methodik/Methods:

Two labeling building blocks based on the piperazine skeleton with either alkyne or azide function were used and an automated module synthesis was evaluated. Further, it was found that the peptide SNEWILPRLPQH show a high affinity to EphB2. Thus, the C-terminus of the peptide was functionalized with alkyne or azide, to retain the high affinity which is constrained of the key sequence SNEW at the N-terminus.

Ergebnisse/Results:

The automated one-step radiosynthesis of two novel building blocks gave the desired piperazine derivatives [¹⁸F]AFP and [¹⁸F]BFP in radiochemical yields of 25-45% (d.c.) within 50 min and a high purity after convenient separation from [¹⁸F]F- and precursor using silica gel cardridges. Radiolabeling of several functionalized SNEW peptides under Click conditions pointed out that [¹⁸F]AFP is only suitable and yielded the radiofluorinated peptide in 10-15 % RCY (d.c.). A by-product was observed when the alkyne building block [¹⁸F]BFP was used due to the competing Glaser coupling. Finally, the peptide was prepared, radiolabeled and purified from the Cu with bispidine on SPPS. This is urgent, otherwise, aggreagtion of the peptide with Cu occur. Finally, the stability of the labeled SNEW peptide was investigated ex vivo showing >80% intact peptide after 1 h. Three more hydrophilic metabolites were observed not determined as [¹⁸F]F-.

Schlussfolgerungen/Conclusions:

With the SNEW peptides highly potent 18F-containing EphB2 inhibitors were found and the labeling on SPPS with [¹⁸F]AFP was successfully established.

With upcoming supercomputer technology, the simulation of laser-driven radiation sources enters the realm of large-scale parameter surveys, interactive simulation and the possibility to add physical effects hitherto impossible to account for.
We present new ideas and techniques to deliver simulations that are closer to experiment and can be better connected to new experimental diagnostics.
We finally show how an integrated experimental and theoretical program is needed to increase the predictive capability of codes and why code validation will be the focus of laser plasma simulations.

Ziel/Aim:

Transglutaminasen und Polyamin-Transporter sind interessante Targets für die funktionelle Bildgebung von Tumoren mittels PET. Zur Adressierung dieser Targets sollen Polyamin-basierte Fluor-18-Tracer Anwendung finden, in denen das Radionuklid über die 4-Fluorbenzoylgruppe (FBz) eingeführt wird. Um die dafür erforderlichen Fluor-19-Analoga zugänglich zu machen, wurde eine Festphasensynthese entwickelt, die die selektive Fluorbenzoylierung an einer Aminogruppe in verschiedenen Polyaminen (u. a. Putrescin, Spermidin, Spermin) ermöglicht. Der etablierte Syntheseweg soll auf die entsprechenden F-18-markierten Analoga übertragen werden.

Methodik/Methods:

Zur selektiven mono-Fluorbenzoylierung wurde das von Wang et al. beschriebene Synthesekonzept angewendet (1). Es beinhaltet den Aufbau des Polyamin-Gerüstes durch Festphasensynthese der entsprechenden Oxopolyamine und deren anschließende Reduktion durch BH₃/THF. Durch Einsatz von Dde und Boc als orthogonale Schutzgruppen und der Möglichkeit, mit 2-Acetyldimedon selektiv primäre Aminogruppen zu schützen, wird die selektive Fluorbenzoylierung verschiedener Aminogruppen ermöglicht.

Ergebnisse/Results:

Durch gezielte Anwendung des genannten Synthesekonzeptes konnten folgende neue Verbindungen in guten bis sehr guten Ausbeuten erhalten werden: N-FBz-Putrescin, N-FBz-Cadaverin, N¹-FBz-3-Oxospermidin, N⁸-FBz-5-Oxospermidin, N¹-FBz-3,8-Dioxospermin, N¹-FBz-Spermidin, N⁴-FBz-Spermidin, N⁸-FBz-Spermidin und N¹-FBz-Spermin. Die Identitäten der Verbindungen wurden NMR-spektroskopisch bestätigt.

Schlussfolgerungen/Conclusions:

Die Festphasensynthese mono-fluorbenzoylierter Polyamine und Oxopolyamine konnte erfolgreich etabliert werden. Durch das Vorliegen der Referenzverbindungen kann nun die Radiosynthese der Fluor-18-Analoga erfolgen, bei denen die 4-Fluorbenzoylgruppe [F-18]SFB-vermittelt angeknüpft wird. Dabei kann vermutlich analog zur Synthese der nichtradioaktiven Verbindungen vorgegangen werden.

Literatur/References:

(1) F. Wang, S. Manku, D. G. Hall, Org. Lett. 2000, 2, 1581-1583

Neptunium (Np) is one of the most important components of nuclear waste to consider for the long-term safety assessment of nuclear waste repositories, due to the increasing en-richment, the long half-life and the high toxicity of Np-237. Hence, great attention is attract-ed to its geochemistry [1]. Among the various geochemical reactions, the molecular pro-cesses occurring at the solid-water interface, e.g. sorption onto mineral phases, surface precipitation, and colloid formation strongly affect the migration behavior of the radioactive contaminant in the environment [2]. Thus, various components of geological materials, such as iron oxides and hydroxides play an important role in regulating the mobility of actinides in aquifers, due to their widespread environmental presence, high sorption capacity and tendency to form coatings on mineral surfaces [3]. In recent years, the sorption behavior of Np(V), the most relevant oxidation state under ambient conditions, onto iron oxides was mainly studied by macroscopic experiments [4]. For a better understanding of the molecular events occurring at the mineral’s surfaces, ATR FT-IR spectroscopy is a useful tool for the in-situ identification of surface species [5]. In addition, time-resolved measurements provide kinetic information on the surface reactions.
In this work, Np(V) sorption on hematite is studied under a variety of environmentally rele-vant sorption conditions by in-situ ATR FT-IR spectroscopy [5]. The IR spectra obtained from the subsequent steps of the experiment, that is (1) conditioning, (2) sorption, and (3) flushing, are shown in Fig. 1.
The absence of significant bands below 1000 cm−1 in the conditioning spectrum demon-strates the stability of the stationary hematite film directly prepared on the ATR crystal’s surface. The bands at 1491 and 1356 cm−1 represent the removal of carbonate by rinsing the hematite film, prepared in air with the CO2 free solution. Upon Np(V) sorption, the band observed at 790 cm−1 is assigned to the antisymmetric stretching vibrational mode (ν3) of the neptunyl ion. The IR spectrum obtained from an aqueous solution at 50 µM Np(V), 0.1 M, pH 6 shows the absorption of ν3(NpVO2) at 818 cm−1. The red shift of ν3 to 790 cm−1 upon sorption can be assigned to an inner-sphere monomeric sorption complex, as previ-ously reported for TiO2, SiO2 and ZnO [5]. The band at 1042 cm−1 is most probably due to surface modes of the mineral oxide provoked by the sorption processes and were already observed for interactions with U(VI), Cs(I) and CO32 [5]. In the flushing stage, a weakly bound species is released from the stationary phase, reflected by a negative band at 795 cm−1 in the respective spectra.
Additional experiments were performed at varied values of pH (5.6 – 12) and ionic strength (0.001 – 0.1) (Fig. 2). Upon increasing the pH from 5.6 to 8.6, no shifts of the bands at 1041 and 790 cm−1 are observed. But the intensities of these spectral features are consid-erably increased at higher pH values indicating an enhanced sorption capacity close to the IEP at pH 9.2. At pH > 10, the aqueous Np(V) speciation changes and NpO2OHaq is formed and distinctly changes the sorption behavior. The band of ν3(NpVO2) is shifted to 773 cm−1. The variation of ionic strength between 0.1 and 0.01 does not change the spectral characteristics. The higher intensities observed at 0.0001 M NaCl can be attributed to contributions of an outer-sphere complex which has to be verified by future experiments.
In summary, the IR spectra evidence the formation of Np surface complexes on hematite which can be easily removed to a considerable extent by flushing with blank solution. From this behavior, the simultaneous formation of an inner-sphere species with con-tributions of an outer-sphere complex is suggested.

[1] Kaszuba, J. P. et al. (1999) Environ. Sci. Technol. 33, 4427-4433.
[2] O'Day, P. A. (1999) Reviews of Geophysics 37, 249-274.
[3] Tochiyama, O. et al. (1996) Radiochim. Acta 73, 191-198.
[4] Brendler, V. et al. (2003) Journal of Contaminant Hydrology 61, 281-291.
[5] Müller, K. et al. (2009) Environ. Sci. Technol. 43, 7665-7670.

Ziel/Aim:

Die Revision von gelockerten Hüft-Pfannen kann den Einsatz von impaktierten Knochen-Allografts (CBA) zur Stabilisierung der Pfanne und zum Auffüllen von Knochendefekten erfordern. Können mittels NaF-PET osteometabolische Veränderungen des CBA zu einem frühen Zeitpunkt nach Revision dokumentiert werden?

Methodik/Methods:

18F-NaF-PETs wurde 1 und 6 Wochen nach Revision durchgeführt. 12 Patienten wurden in die Studie (BfS- und Ethik-Votum) eingeschlossen, 9 Patienten absolvierten PET1+2. Die PET wurden an einem ECAT EXACT HR+ (Siemens/ CTI, USA) durchgeführt. Nach einer 4-min. Transmissionsmessung (Ger-68-Stabquellen) begann mit i.v.-Injektion von 240– 300 MBq F18-NaF eine dynamische Emission über 30 min über den Hüften. Auf einem post-op CT wurden Volumes of interest (VOIs) abgegrenzt (CBA, supracetabulär, os pubis) und nach Fusion von CT- und PET-Datensätze auf das PET übertragen. Die quantitative NaF-Aufnahme der VOIs wurde mit einem irreversiblen 2-Kompartment-Modell berechnet. Die Inputfunktion wurde aus der A. iliaca communis der dynamischen PET bestimmt. Der Parameter km (min-1) repräsentiert den Fluorid-influx in den Knochen.

Ergebnisse/Results:

km des supracetabulären Knochen zeigte auf der operierten Seite von PET1 zu PET2 eine nicht signifikante Zunahme (mean (±SD)) von 0,0491 (±0,0249) auf 0,0678 (±0,0367). Das CBA zeigte eine nicht signifikante Zunahme von 0,0384 (±0,0307) auf 0,0549 (±0,0319). In Zusammenschau mit dem CT war diese Zunahme im Randbereich des CBA lokalisiert und konnte nicht sicher von angrenzendem genuinem Knochengewebe, das visuell bei PET2 eine höhere Stoffwechselaktivität aufwies, getrennt werden.

Schlussfolgerungen/Conclusions:

Die NaF-PET 1 und 6 Wochen nach Revision zeigt eine nicht signifikante Zunahme des Knochenstoffwechsels ipsilateral supracetabulär. In dem CBA können beginnende osteometabolische Veränderungen im Randbereich zum genuinen Knochen nicht ausgeschlossen werden, zur sicheren Dokumentation einer stabilen Durchbauung des CBA wäre eine NaF-PET zu einem späteren Zeitpunkt erforderlich.

Ziel/Aim:

Therapy response varies considerably in advanced cervical carcinoma(ACC). Glucose metabolism and microvascular characteristics of the tumor have been evaluated as biomarkers for identification of patients with poor response before or early during treatment. The combination of both biomarkers for detection of tumor regions with a ‘malignant mismatch’(MM), i.e. strongly increased glycolysis at low blood flow levels, might indicate resistance to therapy. The aim of the present study was to test whether ACC show MM that can be detected by the combination of FDG- and O-15-water-PET.

Methodik/Methods:

Twelve women (27-69y) with locally ACC (FIGO IIB-IIIB; grade G2 n=7, G3 n=5) were included prior to chemo-radiation. Regional blood flow was computed voxel-by-voxel from the O-15-water PET using a weighted integral approach and an image-derived arterial input function. FDG uptake was characterized by SUV. The primary tumor was segmented manually in the CT. A tumor voxel was considered to present MM if the perfusion was lower than the median perfusion in the tumor and the SUV was higher than the median SUV. The absolute total MM volume (aMMV) was obtained by multiplying the number of MM voxels with the voxel volume. The relative MM volume (rMMV) was obtained by dividing the aMMV by the tumor volume.

Ergebnisse/Results:

The volumes of the primary tumors ranged from 54 to 225ml. The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV ranged from 7.7 to 35.5ml, the rMMV from 7.9 to 26.6%. There was no correlation between rMMV and tumor volume (p=0.517). T-testing revealed a tendency (p=0.083) for an association between aMMV and histological grading, aMMV being higher in the G3 than in the G2 tumors. There was no association between grading and rMMV (p=0.888).

Schlussfolgerungen/Conclusions:

ACC show a metabolism/perfusion MM to a strongly variable extent. The mismatch volume seems to be associated with the tumor grade. Evaluation of the prognostic value requires follow-up data in a larger cohort.

Ziel/Aim:

Hypoxie ist charakteristisch für solide Tumoren und trägt maßgeblich zu einem potenziellen Versagen einer Radiochemotherapie (RCT) bei. Ziel dieser prospektiven Studie war es deshalb, den prognostischen Wert der Hypoxie-Bildgebung vor und unter RCT bei Patienten mit lokal fortgeschrittenen Kopf-Hals-Tumoren (KHT) zu explorieren.

Methodik/Methods:

Fünfundzwanzig Patienten mit histologisch gesicherten, unbehandelten KHT im klinischen Stadium III / IV wurden mit der F-18-Misonidazol- (F-MISO-) PET/CT zu 4 Zeitpunkten der kurativ intendierten RCT (initial, 8-10 Gy, 18-20 Gy und 50-60 Gy) untersucht. Parameter wie die maximale Ziel-Hintergrund-Ratio und das Schwellwert-basierte Tumorvolumen bei verschiedenen Ziel-Hintergrund-Rationes, das Tumorvolumen aus der CT sowie typische Basisparameter der initial und bei 40 Gy durchgeführten FDG-PET/CT wurden zu allen Untersuchungszeitpunkten auf ihren prognostischen Wert hin untersucht. Als Endpunkt diente das lokal Progressions-freie Überleben (LPFS). In einer multivariaten Cox-Analyse (einschließlich klinischer Parameter) und mehreren Log-Rank-Tests erfolgte die Prüfung auf signifikante Unterschiede.

Ergebnisse/Results:

Die Parameter aus der F-MISO-PET zeigten eine Assoziation mit dem LPFS-Endpunkt, am strengsten assoziiert waren die Zeitpunkte bei 10 Gy und 20 Gy unter der RCT (p = 0,023-0,048 und 0,042-0,061 in der multivariaten Cox-Analyse). Parameter aus der initialen F-MISO-PET/CT waren nur in der univariaten Analyse signifikant. Weder klinische Parameter, noch CT- oder FDG-PET-basierte Tumorvolumina zeigten eine signifikante Assoziation mit dem LPFS.

Schlussfolgerungen/Conclusions:

Diese prospektive Explorationsstudie demonstriert die prognostische Bedeutung der F-MISO-PET/CT in der frühen Phase der kurativen RCT. F-MISO-Bilder nach 1 oder 2 Wochen RCT (bei 10 bzw. 20 Gy) sind vielversprechend, wenn es um die Selektion der Patienten geht, die von einer Modifikation der Hypoxie oder von einer Dosis-eskalierten Radiatio profitieren könnten. Eine prospektive Validierungsstudie läuft bereits.

The main purpose of Subproject 2 is to further investigate the Key Safety Aspects identified by the Safety Advisory Group of the RAPHAEL project and to contribute to their resolution. Work package 23 targets to fill the knowledge gaps in dust production, deposition and remobilisation. Experimental and (advanced) analytical methods have been adopted to investigate all aspects of dust behaviour.

Aim
There is evidence that α7nAChRs play an important role in cancer and neurodegenerative diseases. Therefore, quantitative imaging of α7nAChRs using PET represents a new approach for investigation of those diseases.
Due to its high target affinity and selectivity [¹⁸F]NS14490, an oxadiazolyl-diazabicyclononane derivative, is a promising radiotracer for α7nAChRs imaging. Manual radiosynthesis of [¹⁸F]NS14490 and its in vivo evaluation in mice were already reported [1]. The subsequent assessment of its imaging potential by dynamic PET studies in piglets and PET/CT studies in tumor-bearing mice required the transfer of the manual synthesis to an automated synthesis module.

Materials and Methods
For dynamic PET studies, the manual radiosynthesis of [¹⁸F]NS14490 [1] was transferred to an automatic synthesis module (Tracerlab FX-N) including azeotropic drying of [¹⁸F]F- with Kryptofix K222/K₂CO₃ in acetonitrile, direct nucleophilic substitution at the precursor, semipreparative HPLC and solid phase extraction. After evaporation the radiotracer was formulated in phosphate buffered saline containing 5% ethanol.
Dynamic PET studies in piglets (female, 15-18 kg) were performed under control and blocking conditions (n=2 each) with a highly selective α7nAChRs ligand (NS6740; bolus: 3 mg kg-¹ h^-1; infusion: 1 mg kg^-1 h^-1) for 4 hours. The metabolism of [¹⁸F]NS14490 in piglets was analyzed by chromatography of plasma samples.
PET/CT studies were performed in tumor-bearing nude mice under control and blocking conditions with NS6740.

Results and Conclusion
During transfer of radiosynthesis into an automated synthesis module, solid phase extraction was challenging. For desorption of the radiotracer from divinyl/polystyrene cartridge, the elution solvent ethanol/acetic acid used in manual synthesis was replaced by acetonitrile/formic acid resulting in more efficient elution, formerly not accomplished. The radiotracer was achieved within 1.25 hours and radiochemical yields (32%), radiochemical purity (> 90%) and specific activity (> 150 GBq μmol_-1) were comparable to the manual synthesis [1]. Brain uptake of [¹⁸F]NS14490 peaked in piglets at 3 min p.i. and is with a value of SUV_max = 0.504 about tenfold higher than in mice. Blocking by NS6740 decreased the specific uptake in brain by 28% (SUV 240 min p.i. 0.174 vs. 0.125 under baseline and blocking conditions, respectively).The metabolic stability of [¹⁸F]NS14490 in piglets is lower than in mice. At 60 min p.i. intact radiotracer represented 30% of plasma activity in piglets compared to 55% in mice.
Preliminary animal PET/CT studies in tumor-bearing mice provide evidence that [¹⁸F]NS14490 may also be suitable for tumor imaging.
[1] Rötering, S. et al. Bioorg. Med. Chem. 2013

Aim
The standard method for fluorine-18 production relies on proton irradiation of oxygen-18 water. Increased demand and costs of O-18 water forced us to consider its re-use for research purposes. After irradiation and F-18 separation the target water is contaminated with radioactive metal ions and organic solvents disturbing its re-use. Therefore, thorough purification is needed before further irradiation is possible. Here, we present two methods for the removal of organic contaminants from used target water.

Materials and Methods
Two different methods were accomplished to oxidize the organic contaminants ethanol and acetone in O-18 water using photo-oxidation (Pen-Ray 254 nm, 5.4 W) [1] and a wet chemical method with KMnO₄ and NaOH. Thereafter vacuum distillation was performed and the target water was validated by gas chromatography, ICP-OES, pH value, conductivity and pycnometry. In addition artificially contaminated O-16 water was used to evaluate the potential of both methods concerning the oxidation of other potential contaminants such as methanol and acetonitrile.
Target irradiations were performed at equal parameters of bombarding (beam current on target 35 μA, 11.7 μAh) at a CYCLONE 18/9 (IBA Molecular, Nirtra^® Fluor L-target (99.9% niobium): 2 mL, target window: Havar alloy, 50 μm).
Radionuclide purity and yields were determined by gamma spectrometry (ORTEC) and an ionization chamber (MED Nuklear-Medizintechnik Dresden GmbH). Produced F-18 was used in nucleophilic substitution reactions in various radiosyntheses of ongoing projects.

Results and Conclusion
Using both purification methods a comparable decrease of organic contaminants from 400 μg mL-1 ethanol and 44 μg mL^-1 acetone to 10 μg mL^-1 – 50 μg mL^-1 ethanol was achieved. Photo-oxidation was approximately 1.5times faster. Important parameters (amount of oxidation agent, temperature, treatment time) for both methods were defined to ensure reproducibility of the radiosyntheses after comparable proton irradiation as done for the purchased target water. We observed a loss of production yield (19%) compared to purchased water due to a lower O-18 concentration. No influence on radionuclide purity or radiochemical yields was observed. Both methods enable a multiple re-cycling of target water for successful F-18 production and application for research purposes. The re-cycling process is limited by the amount of F-18 required for radiosyntheses. Starting from 87% enrichment of O-18 in target water we found 83% enrichement after one cycle allowing reasonable production yields and efficient economical usage of the purchased target water including efforts to minimize the contamination of target water.
[1] DE 29504388 U1, 1995
:

A series of spirocyclic piperidine derivatives were designed and synthesized as σ₁ receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-piperidine] (19) possessed high σ₁ receptor affinity (K_i= 0.79 nM) and excellent σ₁/σ₂ subtype selectivity (350-fold) as well as high σ₁/VAChT selectivity (799-fold). The radiolabeled compound [¹⁸F]19 was synthesized by substitution of the tosylate precursor 24 with [¹⁸F]fluoride, with isolated radiochemical yield of 35–60%, radiochemical purity of >99%, and specific activity of 30–55 GBq/Qmol. Biodistribution studies in ICR mice indicated that [¹⁸F]19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague-Dawley rat demonstrated high accumulation of the radiotracer in brain areas known to express high levels of σ₁ receptors. MicroPET imaging and blocking studies confirmed the specific binding of [¹⁸F]19 to σ₁ receptors in vivo.

Ziel/Aim:

A widely discussed question in PET is the quantitative accuracy (QA) of combined PET/MRI systems. To evaluate QA of the Philips Ingenuity TF PET/MR system we have performed phantom-based evaluations and compared them to measurements on traditional PET systems.

Methodik/Methods:

With the Philips PET/MR a SUV calibration is the standard procedure to calibrate the PET against a dose calibrator (DC). A dynamic scan is started at high activity (≈500 MBq) and run for 7 half-life times. Than a SUV validation with lower activity (≈70 MBq) is run as a static scan for 3 min. We augmented the validation protocol to start at higher activity and to run as a dynamic protocol. To evaluate the clinical relevant QA we have determined typical singles rates (SR) for whole-body (WB) scans. To analyse the influence of the MR-based attenuation (MRAC) we have created an attenuation template (AT) of the phantom and applied it.

Ergebnisse/Results:

The PET-derived activity concentrations and SUVs are significantly lower than calculated from the DC. Using the standard procedure the PET vs. DC ratio is 0.895=10.5% deviation at a level of 73.7 MBq (SR: 14.7 Mcps). For activity increasing from 8.6 to 89.7 MBq the PET/DC ratio decreases from 0.943 to 0.877, corresponding to deviations of 6–12% (SR: 3.8–17.0 Mcps). The use of an AT changes the deviation < 1%. For typical WB scans the SR were found to range from 8.0–16.6 Mcps, corresponding to a underestimates of true activity by 6.8–9.9%.

Schlussfolgerungen/Conclusions:

Our preliminary results show, that QA of the Philips PET/MR in phantoms is off by 6–12%. The effect shows a notable dead-time dependency and cannot be explained by inaccurate MRAC. In addition to the dead-time related variance of ≈3% there remains a systematic error in the calibration, which biases QA of clinical scans by ≈6%. Philips has been informed about the inconsistencies and has acknowledged to provide a fix.

Ziel/Aim:

Quantitative accuracy (QA) of PET parameters like standardised uptake values (SUV) and tracer kinetic rate constants strongly depends on applicability of the (phantom-based) scanner calibration in-vivo. In a previous study we introduced a method for direct in-vivo QA evaluation: for 3 PET(/CT) systems the activity concentrations (Cs) of urine samples measured in a well-counter were compared to the Cs of PET images of the bladder in 56 patients. That study showed a small (7-12%) but systematic underestimation of the true Cs by PET. To address the widely discussed question of QA of combined PET/MRI we have applied this method to our Philips PET/MR.

Methodik/Methods:

Up to now 10 clinical F18-FDG scans have been evaluated. The bladder region was imaged as the last bed position and urine samples collected afterwards. Using the ROVER software, 3D region-of-interests (ROI) of the bladder were delineated by 3 observers. To exclude partial volume effects ROIs were concentrically shrunk by 8–10 mm. Then, Cs were determined in the PET images of the bladder as well as in the urine samples using a cross-calibrated well-counter.

Ergebnisse/Results:

The measured Cs and SUVs are significantly lower in PET/MR than in the well-counter: ratio=0.773±0.035 (mean±SEM) [0.617–0.942] (p=0.00011). After correcting for known (but not yet fixed) inconsistencies in the manufacturer’s scanner calibration of the Philips PET/MR, the ratio is 0.827±0.035 [0.664–1.004] (p=0.0011).

Schlussfolgerungen/Conclusions:

Our preliminary results indicate that the Philips PET/MR underestimates true Cs by ≈17% in-vivo which is ≈7% larger than we observed for PET(/CT). The requirement to apply a correction factor due to inconsistencies in the manufacturer’s provided calibration and similar deviations reported on other PET/MR systems show that vendors of PET/MR systems need to pay special attention regarding QA. In this context, our method might serve as a convenient method to evaluate the actual QA in-vivo.

Ziel/Aim:

The bifunctional chelating agent 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (DMPTACN-COOH) has been coupled to the stabilized bombesin (BBN) derivative [Cha13,Nle14]-BBN(7–14) using the spacer homo-Glu-Ala-Ala, was radiolabeled with the positron emitter copper-64, and the new radiotracer was preclinically characterized.

Methodik/Methods:

The in vitro and in vivo binding characteristics of the Cu-64-labeled bombesin conjugate in gastrin-releasing peptide receptor (GRPR) over-expressing prostate cancer (PC-3) cells/tumors have been evaluated. Biodistribution and metabolism studies were performed in Wistar rats. Small animal PET imaging was carried out to evaluate the biokinetics and tumor accumulation in tumor bearing NMRI nu/nu mice.

Ergebnisse/Results:

The pendant carboxylic group enables this derivative to be conjugated to the N-terminal amino acid residues of the peptide. The resulting radiocopper(II)-ligand complex exhibits high stability. The IC50 value on PC3 cells was 15 nM, the specific binding was confirmed by high uptake in the GRPR-rich pancreas used as reference organ. The peptide showed a good metabolic stability, however, it was fast eliminated by the kidneys. The PC3 tumors in the mice could be clearly imaged with tumor-to-muscle ratios steadily increasing over the time up to 30. The tumor uptake could be blocked by GRP.

Schlussfolgerungen/Conclusions:

Preclinical characterization of the Cu-64-labeled DMPTACN-COOH with incorporation of a single glutamic acid residue within the spacer between bombesin and the radiolabeled complex showed that the probe represents a promising GRPR radiotracer.

Ziel/Aim:

Oncological microtherapy planning, e.g. brachytherapy, based on PET-datasets requires exact quantification and volume definition. The aim of this study was to analyze the influence of current reconstruction algorithms on SUVmax, metabolic volumes and spatial resolution using phantom measurements.

Methodik/Methods:

Measurements were performed on a SIEMENS Biograph mCT 64 using a cylindrical phantom (volume, 6595 ml) containing 4 spheres (14-177 ml) filled with F18-FDG (50 kBq/ml) resulting in 3 background fractions (BGF). Images were reconstructed applying 5 algorithms (3D-OSEM, FBP, FBP-TOF, HD-PET, ultraHD-PET) and two slice thicknesses (3 mm, 5 mm). Segmentation of sphere volumes was performed using semiautomatic tumor-to-background algorithm (ROVER). Spatial resolution was determined using point spread function and fitting of radial activity profiles.

Ergebnisse/Results:

The highest SUVmax deviations were found between ultraHD-PET and FBP-TOF with a mean absolute difference of 1.3 (range, 0.7–2.1) and a corresponding mean relative difference of 13.2% (range, 8.2–20.9%). Metabolic volume difference to reference volume was significantly associated to reconstruction algorithm (p<0.05), background fraction (BGF3 vs BGF1, p<0.001; BGF2 vs BGF1, p=0.1), sphere diameter (p<0.001) but not to slice thickness (p=0.3). Best spatial resolution for BGF1 and BGF2 was detected for ultraHD-PET (5.3/4.5 mm) compared to FBP (6.8/6.6 mm) and 3D-OSEM (5.9/5.4). In contrast, similar spatial resolutions were detected for BGF3 ranging from 5.9 mm (3D-OSEM/FBP) to 6.5 mm (HD-PET). However, TrueX-algorithms (HD-PET, ultraHD-PET) showed substantial edge elevations in radial activity profiles (Gibbs artifacts).

Schlussfolgerungen/Conclusions:

Reconstruction algorithms showed substantial effect on SUVmax. This might be of clinical importance if PET quantification is used in oncological microtherapy planning. The clinical impact of high spatial resolution combined with Gibbs artifacts in TrueX reconstructions has to be analyzed in further trials.

Ziel/Aim:

Arterial input function (IF) determination is traditionally based on arterial blood sampling which is invasive and ill-suited for clinical routine. Alternatively, one can use a population averaged IF determined via blood samples (BSIF) in a separate study. We present a strategy for generation of a population averaged image derived IF (IDIF) in brain investigations.

Methodik/Methods:

An image subvolume enclosing the carotid arteries is manually defined. Further processing is fully automated: 1: peak phase detection of the IF, 2: threshold based, background aware delineation using peak phase optimized for small structure size (~ 5 mm), 3: time activity curve generation, 4: model free recovery coefficient (R) determination 5: recovery and spillover correction according to Cm = R x Ct + (1 - R) x B, Cm/Ct: measured/true signal/IF, B: local background. This method was applied to 48 15-O Water brain studies (acquired with an ECAT HR+ PET). The resulting IFs were averaged, leading to a population averaged image derived IF (IDIF). Gray matter perfusion was computed from the Kety-Schmidt model assuming a partition coefficient in gray matter of 0.9 (f1). Perfusion was also computed using a BSIF from a different institution (f2). f1 and f2 were compared.

Ergebnisse/Results:

f1 and f2 are strongly correlated (Pearson 0.999) and differences are small: (f2-f1)/f2 = (9.7 +/- 0.9)% (mean +/- sd), range 6.7% - 12.7%.

Schlussfolgerungen/Conclusions:

The presented method allows to generate an IDIF which reproduces the results achieved with BSIF with good accuracy. One significant advantage of the new approach is the ease of regeneration of the IDIF for each study group (e.g. after injection and acquisition protocol changes). Due to statistical fluctuations of vessel delineation individual IF determination is not yet possible with this method due to the modest reconstructed resolution of the HR+ data. This might become possible when using state-of-the-art scanners and reconstruction algorithms.

Ziel/Aim:

Moyamoya disease (MMD) is characterized by progressive stenosis or occlusion of the terminal internal carotid arteries with varying development of collaterals requiring the exact characterization of hemodynamics for adequate therapy. The aim of the present study was to compare perfusion SPECT and PET with O-15-water in the same patients.

Methodik/Methods:

Static SPECT and dynamic PET were performed within 1-5 d in 9 MMD patients (18-67 y), both in resting state and after vasodilatory challenge with acetazolamide. The PET data were analyzed with the Watabe reference tissue method for the voxelwise computation of the regional cerebral blood flow. Vasodilatation and resting images were coregistered, stereotactically normalized (SPM8) and smoothed (3d isotropic Gaussian kernel, 20 mm FWHM). The relative cerebrovascular reserve (rCVR) was computed voxel-by-voxel according to the formula rCVR = 100*(s*vasodilatation – resting)/resting. The scale factor (s) was determined to a mean rCVR of 50%. The resulting rCVR maps were assessed visually and using standard ROIS for ACA, MCA and PCA territory (left/ right). A general linear model was used to analyze the effect of modality (SPECT, PET) and territory (ACA, MCA, PCA) on rCVR.

Ergebnisse/Results:

The pattern of rCVR differed significantly between SPECT and PET in 5/9 patients according to visual inspection. PET showed additional or more extended regions with reduced rCVR in these cases. The ROI analysis revealed a significant effect of the modality (p=0.015) and a highly significant modality*territory interaction (p=0.000). PET-rCVR was lower than SPECT-rCVR in the ACA and MCA territory, whereas it was higher in the PCA territory.

Schlussfolgerungen/Conclusions:

There was a substantial difference in the cerebrovascular reserve capacity as measured by SPECT versus PET, both visually and quantitatively. The modality*territory interaction suggests that PET is more accurate than SPECT, as MMD often spares the posterior circulation. However, this has to be confirmed in further studies.

Ziel/Aim:

Der EGFR wird oft überexprimiert in verschiedenen Tumorarten. Daher werden geeignete radionuklidmarkierte EGFR-Liganden für eine gezielte Tumordiagnostik mittels bildgebender Verfahren, z. B. PET, entwickelt. Zwei kürzlich beschriebene EGFR-spezifische Peptide GE11 (1) und D4 (2) sollten mit Chelatoren sowie Spacern so konjugiert werden, dass sie mit dem PET-Nuklid Kupfer-64 markiert werden können. Mit einem der markierten Peptid-Konjugate sollte das Bindungsverhalten (Zeitabhängigkeit und Affinität) an Zellmembranen charakterisiert werden.

Methodik/Methods:

Die Peptide wurden am N-Terminus jeweils mit verschiedenen Spacern sowie mit dem Chelator NOTA verknüpft und anschließend mit Kupfer-64 radiomarkiert. Für Bindunggsassays wurden Membranen der EGFR-exprimierenden A431-Zellen (epidermoides Karzinom) und FaDu-Zellen (Plattenepithelkarzinom) untersucht. Kinetik- und Sättigungs-Assays wurden mit einem Kupfer-64 markierten NOTA-D4-Konjugat ([⁶⁴Cu]Cu-D4-JM) durchgeführt.

Ergebnisse/Results:

Die Peptidkonjugate konnten mit einer Ausbeute von 75-91% hergestellt werden. Bei der Radiomarkierung mit Kupfer-64 konnten spezifische Aktivitäten von bis zu 1000 GBq/µmol erreicht werden, jedoch wurden diese für Bindungsassays auf etwa 30 GBq/µmol eingestellt. Für die Bindung mit [⁶⁴Cu]Cu-D4-JM an A431-Membranen war nach 1 Stunde Assoziation das Bindungsgleichgewicht erreicht, an FaDu-Membranen nach 2 Stunden nicht vollständig. T_Diss½ lag unter 5 min. Die Affinität mittels Sättigung ergab für A431- und für FaDu-Membranen K_d-Werte von 19 bzw. 42 nM.

Schlussfolgerungen/Conclusions:

Mit GE11 und D4 konnten verschiedene EGFR-spezifische Peptid-Konjugate erfolgreich hergestellt werden. Nachdem [⁶⁴Cu]Cu-D4-JM an Zellmembranen untersucht wurde, sind weiterführende Assays an intakten Zellen sowie Tumoraufnahme an Xenograft tragenden Mäusen geplant.

Literatur/References:

(1) Li Z, Zhao R, Wu X et al. FASEB J. 2005, 19(14), 1978-85
(2) Song S, Liu D, Peng JL, et al. Intl. Conf. on Biomedical and Pharmaceutical Engineering 2006, 290-3

Ziel/Aim:

Dem Enzym Lysyloxidase (LOX, EC 1.4.3.13), wird eine Schlüsselfunktion für die Hypoxie-induzierte Tumormetastasierung zugeschrieben (1). Ziel unserer Untersuchungen war die Entwicklung Fluor-18-basierter Radiotracer, die eine In-vivo-Bildgebung dieses Enzyms ermöglichen.

Methodik/Methods:

Das N-terminale Telopeptid der α1-Kette des Typ-I-Kollagens und davon abgeleitete Peptide, die potentielle LOX-Substrate sind, wurden an von den funktionellen Lysinresten verschiedenen Aminogruppen Fluor-18-markiert. Dazu wurde eine Methode entwickelt, die die selektive F-18-Fluorobenzoylierung von Peptiden mit [F-18]SFB ermöglicht (2). Die metabolische Stabilität und Bioverteilung der Radiotracer wurde in normalen männlichen Wistarratten untersucht. Über die Wechselwirkung der verschiedenen Lysin-enthaltenden Peptide mit Atelokollagen wurde durch Oberflächenplasmonenresonanz (SPR) Aufschluss erhalten. Verschiedene Tumorzelllinien wurden in vitro auf die Expression der Lysyloxidase hin untersucht. Die Charakterisierung der Verbindungen erfolgte an A375-Tumormäusen durch dynamisches Kleintier-PET-Imaging und Ex-vivo-Autoradiographie.

Ergebnisse/Results:

Die F-18-fluorbenzoylierten Telopeptidderivate wurden in hohen radiochemischen Ausbeuten und Reinheiten synthetisiert. Alle Peptide zeigten eine gute In-vivo-Stabilität, insbesondere ein cyclisches Derivat des N-Telopeptids. In den Bioverteilungsstudien konnten keine Organanreicherung und eine schnelle renale Eliminierung beobachtet werden. Die Telopeptid-Kollagen-Interaktion konnte erstmals quantitativ untersucht werden.

Schlussfolgerungen/Conclusions:

Geeignete LOX-Substrate wurden Fluor-18-markiert und in vivo eingehend charakterisiert. Trotz ungünstiger Pharmakokinetik infolge schneller renaler Eliminierung zeigen die Tracer das Potential, die LOX-Aktivität in vivo abzubilden.

Literatur/References:

(1) J. T. Erler, K. L. Bennewith, M. Nicolau et al. Nature 2006, 440, 1222-1226
(2) M. Kuchar, M. Pretze, T. Kniess et al. Amino Acids 2012, 43, 1431-1443

Ziel/Aim:

Das Enzym Cyclooxygenase-2 reguliert entzündungsassoziierte Prozesse und wird in vielen Tumoren exprimiert. Die Visualisierung der COX-2 Expression in vivo durch PET könnte daher neue Ansatzpunkte zur Charakterisierung von Tumoren liefern. Um erstmals zu F-18-Fluorethoxy-substituierten COX-2 Inhibitoren zu gelangen und um unterschiedliche COX-2 Inhibitoren mit mono- und bizyklischer Kernstruktur als PET-Tracer zur Verfügung zu stellen, entwickelten wir eine universelle, automatisierte Markierungsmethode.

Methodik/Methods:

Die Entwicklung zweier neuer Fluorethoxy-substituierter Derivate 2-(4-(2-Fluorethoxy)phenyl)-3-(4-(methansulfonyl)phenyl)pyrazolo[1,5-b]pyridazine (A) und 1-(2-Fluorethoxy)-4-(2-(4-(methansulfonyl)phenyl)cyclopent-1-enyl)benzen (B) erfolgte ausgehend von den Ethoxy- bzw. Methoxy-substituierten Derivaten A* und B* (IC50 COX-2: 3 bzw. 5 nM) (1,2). F-18-A und F-18-B wurden in einer automatisierten Syntheseapparatur (TracerlabFX-N) unter optimierten Parametern durch indirekte Markierung der entsprechenden Hydroxyl-Präkursoren mit 1,2-[F-18]Fluorethyltosylat (F-18-C) hergestellt.

Ergebnisse/Results:

Durch enzymatischen Assay wurde für A und B bestätigt, daß die Fluorethylgruppe die COX-2 Inhibitoraktivität nur wenig beeinflusst. Mittels zwei-Stufen/ein-Topf-Synthese inklusive HPLC Reinigung konnte F-18-A ausgehend von [F-18]Fluorid in 70 min mit 7,5% RCA (n=5; zerf.korr.) hergestellt werden (RCR >95%; spezif. Aktivität 27-71 GBq/µmol). In analoger Weise wurde F-18-B in 80 min mit 7,8% RCA (n=7; zerf.korr.) erhalten (RCR 98%; spezif. Aktivität 19-43 GBq/µmol).

Schlussfolgerungen/Conclusions:

Durch die entwickelte automatisierte F-18-Fluorethylierung konnten die COX-2 Inhibitoren F-18-A und F-18-B erfolgreich hergestellt werden, ihre radiopharmakologische Evaluierung findet zur Zeit statt. Die Methode bietet einen effektiven Zugang zur Radiomarkierung von COX-2 Inhibitoren mit Methoxy- bzw. Ethoxy-Funktionen.

Literatur/References:

(1) Beswick et al., Bioorg. Med. Chem. Lett. 2004, 14, 5445.
(2) Wüst et al., Bioorg. Med. Chem. 2008, 16, 7662.

Ziel/Aim:

MR-based attenuation correction in hybrid PET/MR imaging is affected by the reduced transaxial FOV of the MR (40cm) in comparison to that of the PET scanner (60cm) which leads to truncation artifacts in the MR-based attenuation map
(MRMap). In this study we investigate the quantitative influence of truncation artifacts on the reconstructed whole-body PET image volumes and present a new method for truncation compensation (TC).

Methodik/Methods:

Data sets of 17 whole-body FDG patients (BMI 16-38) examined with an Philips Ingenuity PET/MR with arms down were reconstructed using different techniques for TC: (1) no TC (PET-noTC), (2) vendor-provided TC (PET-TC1), (3) newly
developed TC (PET-TC2) based on automatic 3D segmentation of PET-noTC. In all PET volumes, the resulting SUVmax/mean of ROIs in different body regions (e.g. heart, bladder, mediastinum, kidneys, arms etc.) were compared.
Furthermore, a correlation analysis between all voxels in the trunk and truncated arms was performed.

Ergebnisse/Results:

Residual artifacts in the truncation compensated MRMaps were found in 11 (TC1)and 3 (TC2) out of 17 cases. Average SUVmax differences between PET-noTC and PET-TC1/PET-TC2 were: -2.5%/-3.2% (bladder), -4%/-3.4% (kidney),
-3.2%/-3.5% (heart), -2.8/-3.3% (abdomen), -29%/-37% (arms). The correlation analysis showed average SUV deviations of -5% to -1% and -60% to -30% depending on patients' BMI for all voxels in the trunk and truncated arms, respectively.

Schlussfolgerungen/Conclusions:

In whole-body PET imaging, truncation of the arms in the MRMap leads to an average SUV underestimation of ca. 3% in the trunk. In the truncated areas SUV underestimations in the range of 30-60% can be expected. Truncation
compensation based on PET-noTC is straightforward and improves quantification accuracy distinctly. According to our experience the procedure is also well suited for clinical routine.

In order to treat radionuclide sorption processes in natural systems more realistically, temporally and spatially variable distribution coefficients (smart Kd values) are calculated as a function of important environmental parameters such as pH, ionic strength (IS), concentration of dissolved inorganic carbon [DIC], calcium [Ca] and radionuclides [RN]. This smart Kd concept is implemented into the transport code r³t [1].
As a test of the modified code r³t and sensitivity analysis of radionuclide sorption regarding the mentioned environmental parameters, a possible future climate transition (seawater transgression) at Gorleben site / Germany was modelled [2]. Seawater inundation drastically influences the distribution and values of all environmental parameters. Chemical changes cause dissolution or precipitation of calcite and these in turn affect the pH, DIC and Ca concentration. In consequence the Kd values and therewith the transport of radionuclides is impacted.
The results of the calculations are plausible: environ-mental parameters follow expected trends and major dependencies. As a consequence of the low Ca and DIC concentration in seawater, calcite dissolves in the aquifer and causes an increase of the pH. The Kd values change according to the changes in environmental parameters. The pH has the most dominant impact on the smart Kd values for most of the considered RNs, except for Pu and Th, for which the DIC concentration has the strongest impact. Under the assessed conditions for seawater transgressions the smart Kd values of Cs, Ni, Am and Np(V) increase, those of Se(VI) and U(VI) decrease with increasing pH. The smart Kd value particularly of Pu and Th decreases with increasing DIC concentration.

The long-term safety of nuclear waste in deep geological repositories is an important issue in the German society. The migration of actinides and long-lived fission products within the respective host rock and the transport behaviour after a possible release from the repository should be well known. Presence of microorganisms was shown in the subsurface geologic layers, including salt formations, which are considered as potential host rocks /1/. This is of interest because microbes can affect physical and geochemical conditions (e.g. pH, Eh, release of gases) on site and they can also interact with actinides. Important interaction processes are biosorption, bioaccumulation, biotransformation, biomineralization and microbial enhanced chemisorption /2/.
In this work microbial communities were investigated in two different saline environments - the Arava desert in Israel and the salt formation near Gorleben village in Germany.

DESCRIPTION OF THE WORK

Total DNA was recovered from the salt crust (7EY) and from 0 to 3cm depth (10EY) samples of the Arava desert and from one hydrocarbon rich sample C1 from the Gorleben site. Direct molecular analyses of prokaryotic communities were performed by using bacteria specific 16S rRNA gene primers 27F and 1513R /3/ and archaea specific 16S rRNA gene primers 21F and 968R /4/.
Modified R2A medium was used for cultivation of halophilic microbial isolates as described in /5/.

RESULTS

It was demonstrated that the archaeal communities in both 7EY and 10EY samples were predominated by Halobacteriaceae /4/. The recently actualized affiliation of the 16S rRNA gene sequences demonstrated presence of representatives of the genera Haloplanus, Natronomonas, Halobacterium and Halolamina. Several haloarchaeal isolates were cultivated from the salt crust sample 7EY and one of them was characterized as Halobacterium sp. UJ-EY-1 /5/.
On the bacterial phylum level, the samples 7EY and 10EY were predominated by Bacteroidetes, which were accompanied by Firmicutes, Gamma-, Alpha-, and Delta-proteobacteria occurring in a sample-specific way. In addition, differences were found on the species level.
Preliminary results demonstrate that Bacteroidetes are rather abundant in the Gorleben sample C1 where, in addition, Firmicutes are also predominant. Different Proteobacteria are identified in this sample as well. Further investigations of microbial diversity in this and other samples from the Gorleben site are in progress.

At this step of investigation characterization of microbial communities in salt formations representative for potential nuclear waste disposals is ongoing. The next step will be to understand the microbe-actinide interactions of the salt-specific microorganisms. This knowledge will be used to take the microbial activity into account in evaluating the long-term safety of the repositories hosted in salt formations.

REFERENCES

1. Vreeland, R.H., Pisseli A.F., McDonnough, S., Meyers, S. Distribution of halophilic bacteria in a subsurface salt formations. Extremophiles 2, 321-331 (1998).
2. Lloyd, J. R., Macaskie, L. E.: Biochemical basis of microbe-radionuclide interactions. Interactions of Microorganisms with Radionuclides, eds Keith-Roach, M. J., Livens, F. R. Elsevier Science Ltd., 313-342 (2002).
3. Geissler, A., Selenska-Pobell, S.: Addition of U(VI) to a uranium mining waste sample and resulting changes in the indigenous bacterial community. Geobiology 3, 275-285 (2005).
4. Buchvarova, V., Jankowski, U., Flemming, K., Selenska-Pobell S. Halophilic archaeal populations in Arava Desert (Israel) as examined by using direct molecular and cultivation methods FZR-Report 511, p. 34 (2009).
5. Jankowski, U., Flemming, K., Selenska-Pobell, S. Characterization of a Halobacterium sp. isolate cultivated from samples collected from Arava Desert. FZR-Report 511, p. 35 (2009).

Mineral oxides play a decisive role in regulating the mobility of contaminants in the environment because of their widespread occurrence in rocks and soils, their tendency to form coatings on mineral surfaces and their wide-ranging technical applications [1].
Due to its long half-life and its toxicity, Np-237 is considered as a major contaminant of the ecosystem in the long-term safety assesment of nuclear waste repositories. The pentavalent state is environmentally most relevant [2].
For the first time, in-situ Np(V) sorption is comparatively studied on the oxyhydroxides of Fe, Mn, Si and Ti by ATR FT-IR spectroscopy under a variety of environmentally relevant sorption conditions. From the results, the formation of binary inner-sphere complexes on oxides of Si, Mn, Fe and Ti can be derived [3]. In case of ferrihydrite, the formation of an additional ternary Np-carbonato surface species is assumed. In addition, time resolved spectra provide kinetic information on the surface reactions.
[1] Dixon J. B. et al.(1989) Minerals in soil environments. Madison, Wisc.: Soil Science Soc. of America. 1244. [2] Kaszuba J. P. et al. (1999) Env. Sci. & Techn. 33(24), 4427-4433. [3] Müller K. et al. (2009) Env. Sci. & Techn. 43(20): p. 7665-7670

In Middle Europe large deposits of Kupferschiefer involve the Upper Lusatia, the northeastern part of Saxony. The regional Kupferschiefer raised again interest of both industry and science because in this region its copper content constitutes the most important natural copper resource. There is no efficient biotechnological approach applied yet due to the fact that Kupferschiefer is complexly composed comprising different sulfidic minerals, carbonates and organic compounds. Bioleaching, which means the use of microorganisms and their metabolites to extract metals from their ores, reduces costs of high energy input and avoids the usage of toxic chemicals thus benefitting environment (Narayan 2009) and employees.
Raman spectroscopy enables a fast and specific chemical identification of minerals and ores (Hope 2001) as well as the detection of changes e.g. that are caused by oxidation (García-Meza 2012). Also Raman spectroscopic imaging of biotic components such as biofilms has already been performed (Virdis 2012).
We aim to use Raman spectroscopy to investigate the interactions of microorganisms and ore surface: Different polished sections of bornite, chalcopyrite (both from Henderson Mine, Namagualand, South Africa), chalcosite (Ashio, Japan) and copper shale (Polkovice, Poland) were analysed by polarising microscopy to ensure correct spectra assignment. Subsequently identical areas were analysed by Raman imaging using 2D scanning function. After incubation with microorganisms the sections will be investigated again in order to evaluate chemical changes of the ore surfaces, biofilm formation and to monitor bioleaching processes.

Generally, heavy metal contamination of the environment is a result of either natural events like volcanic emissions or human activities such as mining processes. High concentrations of heavy metals are toxic to the majority of organisms. However, several bacteria exhibit surprising strategies to survive in metalliferous environments. These strategies are attractive for novel bio-based resource technologies. Their understanding is the purpose of our research.
Aim of this study was the identification of bacterial methods to accept heavy metals in their environment. Genes that are related to the bacterial heavy metal tolerance strategy were analysed.
Lysinibacillus sphaericus JG-B53, an isolate from the uranium mining waste pile Haberland, was studied using genome sequencing analyses in order to identify strain intrinsic survival strategies like surface (S) layer proteins with metal specific binding affinities and metal specific transporter proteins. The genome of Lysinibacillus sphaericus JG-B53 was sequenced using the Next Generation Sequencing Technology. Bioinformatic analyses of generated data were performed with the Genomics Workbench (CLCbio). The expression of selected genes was studied using mRNA methods. Genes and encoded proteins were characterised with special analysing tools.
The genome of Lysinibacillus sphaericus JG-B53 encodes at least 13 S-layer like proteins and 3 metal ion exporter protein genes for metals that occur in the natural habitat. Their characteristics were analysed with multiple gene and protein analysing programs. Using cDNA analyses the expression of 6 putative S-layer proteins was detected.
Future studies will analyse recombinant S-layer proteins regarding their lattice symmetry and metal binding affinities.

Fine grained ore can only be exploited with finer milling, which results in additional milling costs. The ability to infer the optimal milling parameters and corresponding grades of recovery from microstructural information allows optimal extraction and predicting processing costs and final recovery. The MLA (Mineral Liberation Analyzer) allows quantifying the 2D size of grains in the ore. We have developed a method to predict the effect of milling from milling experiments and MLA-images to the 3D liberation of the value mineral in the ore.

We have designed two novel dendrimers with cyclam cores with appended poly(amido amine) (PAMAM) dendrons, decorated at the periphery with four and eight dansyl chromophores, respectively. The photophysical properties of the dendrimers and their Nd³⁺ complexes have been investigated. The energy-transfer efficiency to the lanthanide ions from these dendrimers has been studied as a function of the generation. It has been observed that an increase in the dendrimer generation as well as the number of amide units enhances the energy transfer to the lanthanide ion.

Die Abteilung „Reaktiver Transport“ der Forschungsstelle Leipzig beschäftigt sich mit dem Migrations-/Sorptionsverhalten von (Schad)stoffen in geologischen Formationen. In aktuellen Projekten werden partikuläre, kolloidale, gelöste und komplexierte, toxische und radiotoxische Stoffe in Batch- und Säulenstudien untersucht. Bei der eingesetzten Radiotracertechnik kommen kurzlebige Radionuklide zum Einsatz. Am Leipziger Zyklotron Cyclone® 18/9 neu implementiert ist die ⁶⁴Cu-Herstellung durch Protonenbeschuss von isotopenangereichertem ⁶⁴Ni via (⁶⁴Ni(p,n)⁶⁴Cu)[1]. Das Target wird durch elektrolytische Abscheidung von ca. 5 mg ⁶⁴Ni auf Goldfolien hergestellt. Die Bestrahlung erfolgt bei einem Protonenstrom von 20 µA bei Strahlzeiten von bis zu 7 Stunden und einer Projektilenergie von ca. 12 MeV. Die chemische Aufarbeitung des bestrahlten Nickels erfolgt durch Ionenchromatographie mit AG1-X8 aus salzsaurer Lösung[2,3]. ⁶⁴Cu wird mit einer radiochemischen Ausbeute von ca. 95 % erhalten. Das wertvolle Targetmaterial (isotopenangereichert auf 95 %) wird mit ~ 90 % Ausbeute wiedergewonnen. Das produzierte Radionuklid wurde erfolgreich zur Visualisierung von Fluidtransport in Geomaterialien mittels PET[4] sowie in der Calixarenkomplexierung[5] eingesetzt.

Literatur:

[1] F. Szelecsényi, G. Blessing, S. M. Qaim, 1993, Appl. Radiat. Isot. 44(3) 575-580.
[2] M. A. Avila-Rodriguez, J. A. Nye, R. J. Nickles, 2007, Appl. Radiat. Isot. 65(10) 1115-1120.
[3] S. Thieme, M. Walther, H.-J. Pietzsch, J. Henninger, S. Preusche, P. Mäding, J. Steinbach, 2012, Appl. Radiat. Isot. 70(4) 602-608.
[4] M. Stoll, Diplomarbeit, in Bearbeitung, Universität Mainz.
[5] M. Poetsch, Masterarbeit, 2012, Universität Leipzig.